Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and test...Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.展开更多
Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunb...Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.展开更多
The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells.In this study,SD rats were divided into the normal chow diet grou...The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells.In this study,SD rats were divided into the normal chow diet group(NCD),high fat diet group(HFD),three treatment groups feeding high-fat diet with naringenin(100,200,400 mg/kg)for 12 weeks.Results indicated that naringenin treatment decreased total cholesterol(TC),triglyceride(TG)and the non-high-density lipoprotein cholesterol(non-HDL-C)levels in serum.Naringenin also alleviated hepatic steatosis and reduced the adipocyte size in the epididymis in high-fat-diet-induced SD rats.In addition,naringenin(25−75μg/mL)decrease TG and TC levels in 3T3 mature adipocytes.The molecular mechanism of naringenin in the treatment of obesity were predicted by using network pharmacology.Real-time PCR analysis results showed that naringenin regulated the expression of lipid metabolism genes.Meanwhile,naringenin increased the AMPK(AMP-activated protein kinase)activity and the expression of AMPK phosphorylated protein in 3T3 mature adipocytes.And the inhibitory effect of naringenin on lipid accumulation in 3T3 adipocytes was abolished by Compound C.Molecular docking results indicated that naringenin could bind to AMPK protein.These results indicated naringenin reduced lipid accumulation through AMPK pathway.展开更多
Phosphoenolpyruvate carboxylase(PEPC;EC 4.1.1.31) catalyses phosphoenolpyruvate(PEP) to yield oxaloacetate,which is involved in protein biosynthesis.Pyruvate kinase(PK;EC 2.7.1.40) catalyzes PEP to yield pyruvat...Phosphoenolpyruvate carboxylase(PEPC;EC 4.1.1.31) catalyses phosphoenolpyruvate(PEP) to yield oxaloacetate,which is involved in protein biosynthesis.Pyruvate kinase(PK;EC 2.7.1.40) catalyzes PEP to yield pyruvate,which is involved in fatty acid synthesis.In this study,five PEPC genes(AhPEPC1,AhPEPC2,AhPEPC3,AhPEPC4,and AhPEPC5) from peanut have been cloned.Using a quantitative real-time RT-PCR approach,the expression pattern of each gene was monitored during the seed development of four peanut varieties(E11,Hebeigaoyou,Naihan 1,and Huayu 26).It was found that these five genes shared similar expression behaviors over the developmental stages of E11 with high expression levels at 30 and 40 d after pegging(DAP);whereas these five genes showed irregular expression patterns during the seed development of Hebeigaoyou.In Naihan 1 and Huayu 26,the expression levels of the five genes remained relatively high in the first stage.The PEPC activity was monitored during the seed development of four peanut varieties and seed oil content was also characterized during whole period of seed development.The PEPC activity followed the oil accumulation pattern during the early stages of development but they showed a significantly negative correlation thereafter.These results suggested that PEPC may play an important role in lipid accumulation during the seed development of four peanut varieties tested.展开更多
Microalgal lipids are regarded as main future feedstock of biofuels for its higher efficiency of accumulation and sus- tainable production. In order to investigate the effect of various nitrogen to phosphorus ratios o...Microalgal lipids are regarded as main future feedstock of biofuels for its higher efficiency of accumulation and sus- tainable production. In order to investigate the effect of various nitrogen to phosphorus ratios on cells growth, chlorophyll content and accumulation of lipids in Dunaliella tertiolecta, experiments were carried out in modified microalgal medium with inorganic nitrogen (nitrate-nitrogen) or organic nitrogen (urea-nitrogen) as the sole nitrogen source at initial N:P ratios ranging from 1:1 to 32:1. The favorable N:P of 16:1 in the nitrate-N or urea-N medium yielded the maximum cell density and specific growth rate. Decrease in chlorophyll content were observed at the N:P of 4:1 in both nitrate-N and urea-N cultures. It was also observed that the maximum lipids concentration was obtained at the N:P of 4:1 in both nitrate and urea nutrient medium. The lipid productivity and lipid content of cultures in the urea-N medium at the N:P of 4: lwere markedly higher than those from cultures with other N:P ratios (p〈 0.05). The results of this work illustrate the possibility that higher ratios of nitrogen to phosphorus have enhancing effect on cells growth of D. tertiolecta. Conversely, higher lipid accumulation is associated with a decrease in chlorophyll content under lower ratios of nitro- gen to phosphorus. The results confirm the hypothesis of this study that a larger metabolic flux has been channeled to lipid accumu- lation in D. tertiolecta cells when the ratios of nitrogen to phosphorus drop below a critical level.展开更多
Calanus sinicus,the dominant copepod in the Yellow Sea,develops a large oil sac in late spring to prepare for over-summering in the Yellow Sea Cold Water Mass(YSCWM).The lipid accumulation mechanism for the initiation...Calanus sinicus,the dominant copepod in the Yellow Sea,develops a large oil sac in late spring to prepare for over-summering in the Yellow Sea Cold Water Mass(YSCWM).The lipid accumulation mechanism for the initiation of over-summering is unknown.Here,we cultured C3 copepodites at four constant temperatures(10,13,16,and 19℃) and at three temperature regimes that mimicked the temperature variations experienced during diurnal vertical migration(10-13℃,10-16℃,and 10-19℃) for 18 days to explore the effects of temperature differences on copepod development and lipid accumulation.C.sinicus stored more lipid at low than at high temperatures.A diurnal temperature difference(10-16℃ and 10-19℃)promoted greater lipid accumulation(1.9-2.1 times) than a constant temperature of either 16℃ or 19℃,by reducing the energy cost at colder temperatures and lengthening copepodite development.Thereafter,the lipid reserve supported gonad development after final molting.Only one male developed in these experiments.This highly female-skewed sex ratio may have been the result of the monotonous microalgae diet fed to the copepodites.This study provides the first evidence that diurnal temperature differences may promote lipid accumulation in C.sinicus,and provides a foundation for future investigations into the mechanisms involved in over-summering in the YSCWM.展开更多
Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or dela...Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.展开更多
The major pathologic hallmark of the alcoholic liver disease(ALD)is the representation of chronic alcohol-induced hepatocyte lipid accumulation.This study aims to investigate the hepatoprotective role of triterpenoids...The major pathologic hallmark of the alcoholic liver disease(ALD)is the representation of chronic alcohol-induced hepatocyte lipid accumulation.This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia(ACT)in chronic alcohol-induced liver injury mice,establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks.In longterm alcohol consumption mice,the significantly lost body weight,increased organ indexes,hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration,showing its hepatoprotective property.ACT suppressed the triglyceride,total cholesterol and low-density lipoprotein levels,and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice.Combining with the pathological observations,ACT displayed an anti-steatosis effects to restrain the progress of ALD.Based on proteomic analysis and enzyme-linked immunosorbent assay,ACT had been confi rmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species.According to further data,ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1αand NF-κB signaling.In summary,ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.展开更多
Lard,a fat rich in saturated fatty acids(SFAs),is regarded as a risk factor for metabolic diseases.In the present study,effect of different lard blended with sunflower oil diets on lipid accumulation in adipose tissue...Lard,a fat rich in saturated fatty acids(SFAs),is regarded as a risk factor for metabolic diseases.In the present study,effect of different lard blended with sunflower oil diets on lipid accumulation in adipose tissue,liver,and serum by mouse model was researched.Body weight,body fat percentage,cross-sectional area of adipocytes,liver triglycerides(TGs),and oil red stained area in mice liver of lard blend sunflower oil(L-SFO)group were significantly lower than those of sunflower oil(SFO)group,whereas no significant differences were observed between mice of lard and L-SFO groups.Serum TG and free fatty acid levels were significantly lower in L-SFO group than in other two groups.Furthermore,data showed that sunflower oil decreased contents of hormonesensitive lipase and carnitine palmitoyl transferase 1(CPT-1)and increased fatty acid synthase activity in liver tissue.A mixture of lard and sunflower oil rather than only sunflower oil or lard might promote body fat loss and reduce lipid accumulation in adipose tissue,serum,and liver by promoting hydrolysis of TG,increasingβ-oxidation of fatty acids.These data suggested that mixing lard and vegetable oil(e.g.sunflower oil)for cooking,or alternate using lard and vegetable oil could be beneficial for reducing body fat.展开更多
<span style="font-family:Verdana;">The Lipid Accumulation Product (LAP) is a clinical marker of visceral obesity and has been proposed as a simple, inexpensive, and accurate tool to estimate cardiovasc...<span style="font-family:Verdana;">The Lipid Accumulation Product (LAP) is a clinical marker of visceral obesity and has been proposed as a simple, inexpensive, and accurate tool to estimate cardiovascular risk and mortality. The aim of this study was to verify the association of LAP with anthropometric, biochemical, visceral adiposity index and IR in adults and the elderly. This single cross-section center clinical study, with experimental, analytical, primary, and observational design, included 210 participants. Anthropometric (Body Mass Index (BMI), Waist Circumference (WC), and Neck Circumference (NC)), LAP, Visceral Adipose Index (VAI), and biochemical parameters (fasting glycemia, insulinemia (to calculate the Homa-IR index), total cholesterol, LDL-c, HDL-c, and triglycerides) were evaluated. The results showed that by separating the sample into three groups (adequate BMI and WC, adequate BMI and elevated WC, and elevated BMI and WC), the group with high BMI and WC showed a high value of LAP and VAI compared to the other groups, with a significant difference. Still, the data show a positive and significant correlation when relating the LAP with VAI, HOMA-IR, BMI, WC, NC, total cholesterol, triglycerides, and Diastolic Blood Pressure. It also showed an inversely proportional relationship when associating LAP with HDL-c (p < 0.0001). Thus, we show that LAP is closely related to visceral adiposity, IR, altered lipid parameters, and blood pressure, especially diastolic in the patients included in our study. For these reasons, we suggest that LAP is a reliable indicator of promising visceral adiposity for early detection of cardiovascular risk in the adult and senior population.</span>展开更多
The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs.The bile acids with varying levels within two types of pigs were found and then in vitro exper...The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs.The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation.Fourteen pigs,including seven lean and seven obese pigs with body weights of approximately 80 kg,were fed the same diet at an amount approximately equivalent to 3%of their respective body weights daily for 42 d.In vitro,3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium.Then,bile acids were added to mature adipocytes for 4 d.The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs(P<0.05).According to the results of gut microbial function prediction,the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig.Sixty-five bile acids were further screened by metabolomics,of which 4 were upregulated(P<0.05)and 2 were downregulated(P<0.05)in obese pigs compared to lean pigs.The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-β-D-glucuronide(CDCA-3Gln)andω-muricholic acid(ω-MCA)had a negative correlation with abdominal fat weight and abdominal fat rate,while isoallolithocholic acid(IALCA)was positively associated with crude fat in the liver and abdominal fat rate.There was a positive correlation between loin muscle area and CDCA-3Gln andω-MCA(P<0.05),however,IALCA and 3-oxodeoxycholic acid(3-oxo-DCA)were negatively associated with loin eye muscle area(P<0.05).Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma(PPARG)and the number of lipid droplets(P<0.05),promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro.In conclusion,the concentration of bile acids,especially gut microbiota related-secondary bile acids,in obese pigs was different from that in lean pigs,which may contribute to lipid accumulation within obese pigs.展开更多
Background:The mechanism of metabolism reprogramming is an unsolved problem in clear cell renal cell carcinoma(ccRCC).Recently,it was discovered that the Hippo pathway altered tumor metabolism and promoted tumor progr...Background:The mechanism of metabolism reprogramming is an unsolved problem in clear cell renal cell carcinoma(ccRCC).Recently,it was discovered that the Hippo pathway altered tumor metabolism and promoted tumor progression.Thus,this study aimed at identifying key regulators of metabolism reprogramming and the Hippo pathway in ccRCC and pinpointing potential therapeutic targets for ccRCC patients.Methods:Hippo-related gene sets and metabolic gene sets were used to screen potential regulators of the Hippo pathway in ccRCC.Public databases and samples from patients were applied to investigate the association of dihydrolipoamide branched chain transacylase E2(DBT)with ccRCC and Hippo signaling.The role of DBT was confirmed by gain or loss of function assays in vitro and in vivo.Mechanistic results were yielded by luciferase reporter assay,immunoprecipitation,mass spectroscopy,and mutational studies.Results:DBT was confirmed as a Hippo-related marker with significant prognostic predictive value,and its downregulationwas caused bymethyltransferaselike-3(METTL3)-mediated N6-methyladenosine(m6A)modification in ccRCC.Functional studies specified DBT as a tumor suppressor for inhibiting tumor progression and correcting the lipid metabolism disorder in ccRCC.Mechanistic findings revealed that annexin A2(ANXA2)interacted with the lipoyl-binding domain of DBT to activate Hippo signaling which led to decreased nuclear localization of yes1-associated transcriptional regulator(YAP)and transcriptional repression of lipogenic genes.Conclusions:This study demonstrated a tumor-suppressive role for the DBT/ANXA2/YAP axis-regulated Hippo signaling and suggested DBT as a potential target for pharmaceutical intervention in ccRCC.展开更多
Arrhythmogenic cardiomyopathy(ACM),a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes,accounts for 20%of sudden cardiac death and lacks effective treatment.It is often caused by mut...Arrhythmogenic cardiomyopathy(ACM),a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes,accounts for 20%of sudden cardiac death and lacks effective treatment.It is often caused by mutations in desmosome proteins,with Desmoglein-2(DSG2)mutations as a common etiology.However,the mechanism underlying the accumulation of fibrofatty in ACM remains unknown,which impedes the development of curative treatment.Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2(CS-Dsg2^(-/-)).Heart failure and cardiac lipid accumulation were observed in CSDsg2^(-/-)mice.We demonstrated that these phenotypes were caused by decline of fatty acid(FA)β-oxidation resulted from impaired mammalian target of rapamycin(m TOR)signaling.Rapamycin worsened while overexpression of m TOR and 4EBP1 rescued the FAβ-oxidation pathway in CS-Dsg2^(-/-)mice.Reactivation of PPARa by fenofibrate or AAV9-Ppara significantly alleviated the lipid accumulation and restored cardiac function.Our results suggest that impaired m TOR-4EBP1-PPARa-dependent FAβ-oxidation contributes to myocardial lipid accumulation in ACM and PPARa may be a potential target for curative treatment of ACM.展开更多
Alcoholic liver disease(ALD)is a growing global health concern,and its early pathogenesis includes steatosis and steatohepatitis.Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD.Eviden...Alcoholic liver disease(ALD)is a growing global health concern,and its early pathogenesis includes steatosis and steatohepatitis.Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD.Evidence shows that puerarin(Pue),an isoflavone isolated from Pueraria lobata,exerts cardio-protective,neuroprotective,anti-inflammatory,antioxidant activities.However,the therapeutic potential of Pue on ALD remains unknown.In the study,both the NIAAA model and ethanol(EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism.The results showed that Pue(100 mg·kg^(−1))attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c,TNF-α,IL-6 and IL-1β,compared with silymarin(Sil,100 mg·kg^(−1)).In vitro results were consistent with in vivo results.Mechanistically,Pue might suppress liver lipid accumulation and inflammation by regulating MMP8.In conclusion,Pue might be a promising clinical candidate for ALD treatment.展开更多
This study aims to investigate the impact of hepatocyte nuclear factor 1β(HNF1b)on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum(...This study aims to investigate the impact of hepatocyte nuclear factor 1β(HNF1b)on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum(PAOA-flavone)-promoted small ubiquitin-related modifier(SUMO)modification in the atheroprotective efficacy of HNF1b.HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics,dual-luciferase reporter gene assay,and chromatin immunoprecipitation.HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages,leading to a depression in atherosclerotic plaque formation in low-density lipoprotein(LDL)receptor-deficient(LDLR−/−)mice.Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification.The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages.PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1(SAE1)expression and SAE1-catalyzed SUMOylation of the HNF1b protein,which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient(ApoE−/−)mice.Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration.In summary,HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis.This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated,SAE1-catalyzed SUMOylation of the HNF1b protein.展开更多
Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug ...Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug development based on glucokinase(GK)activation is an important strategy for lowering blood glucose.This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice.Materials and methods:Mice were fed with a high-fat diet(HFD)for 16 weeks to induce obesity,followed by a GK activator(GKA,AZD1656)or vehicle treatment by gavage for 4 weeks.The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests.Hepatic lipid accumulation was assessed by hematoxylin and eosin staining,Oil Red O staining,and transmission electron microscopy.The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis,with a mechanistic study in mouse livers in vivo and AML12 cells in vitro.Results:GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation.Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase(PERK)-unfolded protein response(UPR)pathway activations in GKA-treated HFD-fed mice.Inhibition of the ACC activity,which is an important protein in lipogenesis,attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro.Conclusions:GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression,which subsequently activated the hepatic PERK-UPR signaling pathway.展开更多
Objective:To evaluate the effect of high concentration of chlorogenic acid(CGA)on non-alcoholic fatty liver disease(NAFLD)in normal and oleic acid(OA)treated Hep G2 cells,as well as the underlying mechanism inv...Objective:To evaluate the effect of high concentration of chlorogenic acid(CGA)on non-alcoholic fatty liver disease(NAFLD)in normal and oleic acid(OA)treated Hep G2 cells,as well as the underlying mechanism involved in the fat accumulation,oxidative stress and insulin resistance(IR)induced by CGA treatment.Methods:OA(0.5 mmol/L)induced hepatic steatosis was established in Hep G2 cells as an in vitro model of NAFLD.The normal and OA-treated Hep G2 cells were treated by CGA(0,0.5,1,and 2 mmol/L)for24 h,then cellular lipid droplets,reactive oxygen species(ROS),and glucose uptake were evaluated by Oil Red O staining and cellular biochemical assays,respectively.Signaling pathways involved in adipogenesis including SREBP-1c and PNPLA3,oxidative stress,and IR including CYP2E1 and CYP4A,were investigated by Western blot and RT-q PCR.Results:CGA(0.5,1,and 2 mmol/L)treatment increased the cellular lipid droplets and the expression of SREBP-1c and PNPLA3 in the tested cells.Additionally,2-NBDG uptake was significantly increased,whereas the cellular ROS and protein levels of CYP2E1 and CYP4A were significantly decreased in OA-treated cells.Conclusion:Our results suggest that high concentrations of CGA ameliorated OA-induced oxidative damage and IR likely by inhibiting the expression of CYP2E1 and CYP4A,and promoted lipid accumulation by inducing the expression of SREBP-1c and PNPLA3 in the tested cells.展开更多
Background and Aims:Lipid accumulation is the major characteristic of non-alcoholic fatty liver disease,the prevalence of which continues to rise.We aimed to investigate the effects and mechanisms of icaritin on lipid...Background and Aims:Lipid accumulation is the major characteristic of non-alcoholic fatty liver disease,the prevalence of which continues to rise.We aimed to investigate the effects and mechanisms of icaritin on lipid accumulation.Methods:Cells were treated with icaritin at 0.7,2.2,6.7,or 20μM for 24 h.The effects on lipid accumulation in L02 and Huh-7 cells were detected by Bodipy and oil red O staining,respectively.Mitochondria biogenesis of L02 cells was detected by MitoTracker Orange staining.Glucose uptake and adenosine triphosphate content of 3T3-L1 adipocytes and C2C12 myotubes were detected.The expression levels of proteins in the adenosine 5′-monophosphate-activated protein kinase(AMPK)signaling pathway,biomarkers of autophagy,and mitochondria biogenesis were measured by western blotting.LC3 puncta were detected by immunofluorescence.Results:Icaritin significantly attenuated lipid accumulation in L02 and Huh-7 cells and boosted the mitochondria biogenesis of L02 cells.Icaritin enhanced glucose uptake,decreased adenosine triphosphate content,and activated the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes.Icaritin boosted autophagy and also enhanced the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts.However,icaritin decreased autophagy and promoted mitochondria biogenesis in 3T3-L1 adipocytes and C2C12 myotubes.Conclusions:Icaritin attenuates lipid accumulation by increasing energy expenditure and regulating autophagy by activating the AMPK pathway.展开更多
This study compared the growth and lipid accumulation properties of two oleaginous microalgae, namely, Scenedesmus sp. LX1 and Chlorella sp. HQ, under different nutrient conditions. Both algal species obtained the hig...This study compared the growth and lipid accumulation properties of two oleaginous microalgae, namely, Scenedesmus sp. LX1 and Chlorella sp. HQ, under different nutrient conditions. Both algal species obtained the highest biomass, lipid content and lipid yield under low-nutrient conditions (mBGll medium). The biomass, lipid content and lipid yield of Scenedesmus sp. LX1 were 0.42g·L^-1, 22.5% and 93.8mg·L^-1, respectively. These values were relatively higher than those of Chlorella sp. HQ (0.30g·L^-1, 17.1% and 51.3mg·L^-1, respectively). These algae were then cultivated in an SE medium that contained more nutrients; as a result, the biomass and lipid yield of Scenedesmus sp. LX1 reduced more significantly than those of Chlorella sp. HQ. Opposite results were observed in lipid and triacylglycerols (TAGs) contents. The cell sizes of both algal species under low-nutrient conditions were larger than those under high-nutrient conditions. Chlorella sp. HQ cells did not aggregate, but Scenedesmus sp. LX1 cells flocculated easily, particularly under low-nutrient conditions. In summary, low-nutrient conditions favour the growth and lipid production of both algae, but Scenedesmus sp. LX1 outperforms Chlorella sp. HQ.展开更多
As significant differences in cellular physiology, metabolic potential and genetics occur among strains with morphological similarity, the screening of appropriate microalgae species for effective CO2 fixation and bio...As significant differences in cellular physiology, metabolic potential and genetics occur among strains with morphological similarity, the screening of appropriate microalgae species for effective CO2 fixation and biodiesel production is extremely critical. In this study, ten strains of Chlorella were cultivated in municipal wastewater influent(MWI) and their tolerance for MWI, CO2 fixation efficiency and lipid productivity were assessed. The results showed that the biomass concentrations of four strains(Chlorella vulgaris, Chlorella64.01, Chlorella regularis var. minima and Chlorella sp.) were significantly higher than other strains. When the cultivation systems were aerated with 10% CO2, Chlorella sp. showed the highest CO2 fixation efficiency(35.51%), while the highest lipid accumulation(58.48%) was observed with C. vulgaris. Scanning electron microscopy images revealed that the cells of both Chlorella sp. and C. vulgaris kept their normal morphologies after 15 day batch culture.These findings indicated that Chlorella sp. and C. vulgaris have fairly good tolerance for MWI,and moreover, Chlorella sp. was appropriate for CO2 fixation while C. vulgaris represented the highest potential for producing biodiesel.展开更多
基金supported by the priority academic program development of Jiangsu Higher education institutionsthe National Natural Science Foundation of China [31801538, 32072200]China Postdoctoral Science Foundation[2019M651747].
文摘Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.
基金supported by Korea Institute of Marine Science&Technology Promotion(KIMST)funded by the Ministry of Oceans and Fisheries,Korea(20220488)。
文摘Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.
文摘The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells.In this study,SD rats were divided into the normal chow diet group(NCD),high fat diet group(HFD),three treatment groups feeding high-fat diet with naringenin(100,200,400 mg/kg)for 12 weeks.Results indicated that naringenin treatment decreased total cholesterol(TC),triglyceride(TG)and the non-high-density lipoprotein cholesterol(non-HDL-C)levels in serum.Naringenin also alleviated hepatic steatosis and reduced the adipocyte size in the epididymis in high-fat-diet-induced SD rats.In addition,naringenin(25−75μg/mL)decrease TG and TC levels in 3T3 mature adipocytes.The molecular mechanism of naringenin in the treatment of obesity were predicted by using network pharmacology.Real-time PCR analysis results showed that naringenin regulated the expression of lipid metabolism genes.Meanwhile,naringenin increased the AMPK(AMP-activated protein kinase)activity and the expression of AMPK phosphorylated protein in 3T3 mature adipocytes.And the inhibitory effect of naringenin on lipid accumulation in 3T3 adipocytes was abolished by Compound C.Molecular docking results indicated that naringenin could bind to AMPK protein.These results indicated naringenin reduced lipid accumulation through AMPK pathway.
基金supported by the China Agriculture Research System (CARS-14)the National Natural Science Foundation of China (31000728,31100205)+2 种基金the Natural Science Fundation of Shangdong Province,China(ZR2009DQ004,ZR2011CQ036)the Promotive Research Fund for Young and Middle-Aged Scientisits of Shandong Province,China (BS2010NY023)the Qingdao Municipal Science and Technology Plan Project,China (11-2-4-9-(3)-jch,11-2-3-26-nsh)
文摘Phosphoenolpyruvate carboxylase(PEPC;EC 4.1.1.31) catalyses phosphoenolpyruvate(PEP) to yield oxaloacetate,which is involved in protein biosynthesis.Pyruvate kinase(PK;EC 2.7.1.40) catalyzes PEP to yield pyruvate,which is involved in fatty acid synthesis.In this study,five PEPC genes(AhPEPC1,AhPEPC2,AhPEPC3,AhPEPC4,and AhPEPC5) from peanut have been cloned.Using a quantitative real-time RT-PCR approach,the expression pattern of each gene was monitored during the seed development of four peanut varieties(E11,Hebeigaoyou,Naihan 1,and Huayu 26).It was found that these five genes shared similar expression behaviors over the developmental stages of E11 with high expression levels at 30 and 40 d after pegging(DAP);whereas these five genes showed irregular expression patterns during the seed development of Hebeigaoyou.In Naihan 1 and Huayu 26,the expression levels of the five genes remained relatively high in the first stage.The PEPC activity was monitored during the seed development of four peanut varieties and seed oil content was also characterized during whole period of seed development.The PEPC activity followed the oil accumulation pattern during the early stages of development but they showed a significantly negative correlation thereafter.These results suggested that PEPC may play an important role in lipid accumulation during the seed development of four peanut varieties tested.
基金partially supported by Tianjin Marine Revitalization Plan of Science and Technology (No.KJXH2013-16) from Tianjin Oceanic Administration,China
文摘Microalgal lipids are regarded as main future feedstock of biofuels for its higher efficiency of accumulation and sus- tainable production. In order to investigate the effect of various nitrogen to phosphorus ratios on cells growth, chlorophyll content and accumulation of lipids in Dunaliella tertiolecta, experiments were carried out in modified microalgal medium with inorganic nitrogen (nitrate-nitrogen) or organic nitrogen (urea-nitrogen) as the sole nitrogen source at initial N:P ratios ranging from 1:1 to 32:1. The favorable N:P of 16:1 in the nitrate-N or urea-N medium yielded the maximum cell density and specific growth rate. Decrease in chlorophyll content were observed at the N:P of 4:1 in both nitrate-N and urea-N cultures. It was also observed that the maximum lipids concentration was obtained at the N:P of 4:1 in both nitrate and urea nutrient medium. The lipid productivity and lipid content of cultures in the urea-N medium at the N:P of 4: lwere markedly higher than those from cultures with other N:P ratios (p〈 0.05). The results of this work illustrate the possibility that higher ratios of nitrogen to phosphorus have enhancing effect on cells growth of D. tertiolecta. Conversely, higher lipid accumulation is associated with a decrease in chlorophyll content under lower ratios of nitro- gen to phosphorus. The results confirm the hypothesis of this study that a larger metabolic flux has been channeled to lipid accumu- lation in D. tertiolecta cells when the ratios of nitrogen to phosphorus drop below a critical level.
基金Supported by the State Key Program of National Natural Science Foundation of China(No.41230963)the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDA11020305)the NSFC-Shandong Joint Fund for Marine Ecology and Environmental Sciences(No.U1406403)
文摘Calanus sinicus,the dominant copepod in the Yellow Sea,develops a large oil sac in late spring to prepare for over-summering in the Yellow Sea Cold Water Mass(YSCWM).The lipid accumulation mechanism for the initiation of over-summering is unknown.Here,we cultured C3 copepodites at four constant temperatures(10,13,16,and 19℃) and at three temperature regimes that mimicked the temperature variations experienced during diurnal vertical migration(10-13℃,10-16℃,and 10-19℃) for 18 days to explore the effects of temperature differences on copepod development and lipid accumulation.C.sinicus stored more lipid at low than at high temperatures.A diurnal temperature difference(10-16℃ and 10-19℃)promoted greater lipid accumulation(1.9-2.1 times) than a constant temperature of either 16℃ or 19℃,by reducing the energy cost at colder temperatures and lengthening copepodite development.Thereafter,the lipid reserve supported gonad development after final molting.Only one male developed in these experiments.This highly female-skewed sex ratio may have been the result of the monotonous microalgae diet fed to the copepodites.This study provides the first evidence that diurnal temperature differences may promote lipid accumulation in C.sinicus,and provides a foundation for future investigations into the mechanisms involved in over-summering in the YSCWM.
文摘Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.
基金This research was funded by the National Key Research&Development Program of China(grant number:2018YFE0107800)the Special Projects of the Cooperation between Jilin University and Jilin Province(grant number:SXGJXX2017-1)+1 种基金the Science and Technology Develop Project in Jilin Province of China under grant(No.20191102027YY,20200708091YY and 20200708068YY)Research and Cultivation Project for Young Teachers of Jiangxi Medical College,Nanchang University(No.PY201901).
文摘The major pathologic hallmark of the alcoholic liver disease(ALD)is the representation of chronic alcohol-induced hepatocyte lipid accumulation.This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia(ACT)in chronic alcohol-induced liver injury mice,establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks.In longterm alcohol consumption mice,the significantly lost body weight,increased organ indexes,hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration,showing its hepatoprotective property.ACT suppressed the triglyceride,total cholesterol and low-density lipoprotein levels,and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice.Combining with the pathological observations,ACT displayed an anti-steatosis effects to restrain the progress of ALD.Based on proteomic analysis and enzyme-linked immunosorbent assay,ACT had been confi rmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species.According to further data,ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1αand NF-κB signaling.In summary,ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.
基金This research was funded by the National Key Research and Development Program of China(2016YDF0501200).
文摘Lard,a fat rich in saturated fatty acids(SFAs),is regarded as a risk factor for metabolic diseases.In the present study,effect of different lard blended with sunflower oil diets on lipid accumulation in adipose tissue,liver,and serum by mouse model was researched.Body weight,body fat percentage,cross-sectional area of adipocytes,liver triglycerides(TGs),and oil red stained area in mice liver of lard blend sunflower oil(L-SFO)group were significantly lower than those of sunflower oil(SFO)group,whereas no significant differences were observed between mice of lard and L-SFO groups.Serum TG and free fatty acid levels were significantly lower in L-SFO group than in other two groups.Furthermore,data showed that sunflower oil decreased contents of hormonesensitive lipase and carnitine palmitoyl transferase 1(CPT-1)and increased fatty acid synthase activity in liver tissue.A mixture of lard and sunflower oil rather than only sunflower oil or lard might promote body fat loss and reduce lipid accumulation in adipose tissue,serum,and liver by promoting hydrolysis of TG,increasingβ-oxidation of fatty acids.These data suggested that mixing lard and vegetable oil(e.g.sunflower oil)for cooking,or alternate using lard and vegetable oil could be beneficial for reducing body fat.
文摘<span style="font-family:Verdana;">The Lipid Accumulation Product (LAP) is a clinical marker of visceral obesity and has been proposed as a simple, inexpensive, and accurate tool to estimate cardiovascular risk and mortality. The aim of this study was to verify the association of LAP with anthropometric, biochemical, visceral adiposity index and IR in adults and the elderly. This single cross-section center clinical study, with experimental, analytical, primary, and observational design, included 210 participants. Anthropometric (Body Mass Index (BMI), Waist Circumference (WC), and Neck Circumference (NC)), LAP, Visceral Adipose Index (VAI), and biochemical parameters (fasting glycemia, insulinemia (to calculate the Homa-IR index), total cholesterol, LDL-c, HDL-c, and triglycerides) were evaluated. The results showed that by separating the sample into three groups (adequate BMI and WC, adequate BMI and elevated WC, and elevated BMI and WC), the group with high BMI and WC showed a high value of LAP and VAI compared to the other groups, with a significant difference. Still, the data show a positive and significant correlation when relating the LAP with VAI, HOMA-IR, BMI, WC, NC, total cholesterol, triglycerides, and Diastolic Blood Pressure. It also showed an inversely proportional relationship when associating LAP with HDL-c (p < 0.0001). Thus, we show that LAP is closely related to visceral adiposity, IR, altered lipid parameters, and blood pressure, especially diastolic in the patients included in our study. For these reasons, we suggest that LAP is a reliable indicator of promising visceral adiposity for early detection of cardiovascular risk in the adult and senior population.</span>
基金funded by National Natural Science Foundation of China (31730091).
文摘The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs.The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation.Fourteen pigs,including seven lean and seven obese pigs with body weights of approximately 80 kg,were fed the same diet at an amount approximately equivalent to 3%of their respective body weights daily for 42 d.In vitro,3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium.Then,bile acids were added to mature adipocytes for 4 d.The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs(P<0.05).According to the results of gut microbial function prediction,the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig.Sixty-five bile acids were further screened by metabolomics,of which 4 were upregulated(P<0.05)and 2 were downregulated(P<0.05)in obese pigs compared to lean pigs.The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-β-D-glucuronide(CDCA-3Gln)andω-muricholic acid(ω-MCA)had a negative correlation with abdominal fat weight and abdominal fat rate,while isoallolithocholic acid(IALCA)was positively associated with crude fat in the liver and abdominal fat rate.There was a positive correlation between loin muscle area and CDCA-3Gln andω-MCA(P<0.05),however,IALCA and 3-oxodeoxycholic acid(3-oxo-DCA)were negatively associated with loin eye muscle area(P<0.05).Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma(PPARG)and the number of lipid droplets(P<0.05),promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro.In conclusion,the concentration of bile acids,especially gut microbiota related-secondary bile acids,in obese pigs was different from that in lean pigs,which may contribute to lipid accumulation within obese pigs.
基金National Natural Science Foundation of China,Grant/Award Numbers:81874090,82202911National Key Scientific Instrument and Equipment Development Project,Grant/Award Number:81927807。
文摘Background:The mechanism of metabolism reprogramming is an unsolved problem in clear cell renal cell carcinoma(ccRCC).Recently,it was discovered that the Hippo pathway altered tumor metabolism and promoted tumor progression.Thus,this study aimed at identifying key regulators of metabolism reprogramming and the Hippo pathway in ccRCC and pinpointing potential therapeutic targets for ccRCC patients.Methods:Hippo-related gene sets and metabolic gene sets were used to screen potential regulators of the Hippo pathway in ccRCC.Public databases and samples from patients were applied to investigate the association of dihydrolipoamide branched chain transacylase E2(DBT)with ccRCC and Hippo signaling.The role of DBT was confirmed by gain or loss of function assays in vitro and in vivo.Mechanistic results were yielded by luciferase reporter assay,immunoprecipitation,mass spectroscopy,and mutational studies.Results:DBT was confirmed as a Hippo-related marker with significant prognostic predictive value,and its downregulationwas caused bymethyltransferaselike-3(METTL3)-mediated N6-methyladenosine(m6A)modification in ccRCC.Functional studies specified DBT as a tumor suppressor for inhibiting tumor progression and correcting the lipid metabolism disorder in ccRCC.Mechanistic findings revealed that annexin A2(ANXA2)interacted with the lipoyl-binding domain of DBT to activate Hippo signaling which led to decreased nuclear localization of yes1-associated transcriptional regulator(YAP)and transcriptional repression of lipogenic genes.Conclusions:This study demonstrated a tumor-suppressive role for the DBT/ANXA2/YAP axis-regulated Hippo signaling and suggested DBT as a potential target for pharmaceutical intervention in ccRCC.
基金supported by grants from the National Natural Science Foundation of China(82170818,81770794,31401001)the Fundamental Research Funds for the Central Universities(21620423,China)the Science and Technology Project of Zhuhai(20191210E030072,China)。
文摘Arrhythmogenic cardiomyopathy(ACM),a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes,accounts for 20%of sudden cardiac death and lacks effective treatment.It is often caused by mutations in desmosome proteins,with Desmoglein-2(DSG2)mutations as a common etiology.However,the mechanism underlying the accumulation of fibrofatty in ACM remains unknown,which impedes the development of curative treatment.Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2(CS-Dsg2^(-/-)).Heart failure and cardiac lipid accumulation were observed in CSDsg2^(-/-)mice.We demonstrated that these phenotypes were caused by decline of fatty acid(FA)β-oxidation resulted from impaired mammalian target of rapamycin(m TOR)signaling.Rapamycin worsened while overexpression of m TOR and 4EBP1 rescued the FAβ-oxidation pathway in CS-Dsg2^(-/-)mice.Reactivation of PPARa by fenofibrate or AAV9-Ppara significantly alleviated the lipid accumulation and restored cardiac function.Our results suggest that impaired m TOR-4EBP1-PPARa-dependent FAβ-oxidation contributes to myocardial lipid accumulation in ACM and PPARa may be a potential target for curative treatment of ACM.
基金the National Natural Science Foundation of China(No.31900285)the Natural Science FoundationofAnhuiProvince(Nos.2108085QH309and 2208085MH203)Anhui Medical University"Three Complete Education"Comprehensive Reform Pilot Project(No.2021xsqyr05)。
文摘Alcoholic liver disease(ALD)is a growing global health concern,and its early pathogenesis includes steatosis and steatohepatitis.Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD.Evidence shows that puerarin(Pue),an isoflavone isolated from Pueraria lobata,exerts cardio-protective,neuroprotective,anti-inflammatory,antioxidant activities.However,the therapeutic potential of Pue on ALD remains unknown.In the study,both the NIAAA model and ethanol(EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism.The results showed that Pue(100 mg·kg^(−1))attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c,TNF-α,IL-6 and IL-1β,compared with silymarin(Sil,100 mg·kg^(−1)).In vitro results were consistent with in vivo results.Mechanistically,Pue might suppress liver lipid accumulation and inflammation by regulating MMP8.In conclusion,Pue might be a promising clinical candidate for ALD treatment.
基金supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region,China (No.2019JJA140728)the Horizontal Cooperation Project with Hunan Mingshun Pharmaceutical Co.,Ltd. (No.2021GLHX02)the Guangxi Province Postgraduate Co-training Base for Cooperative Innovation in Basic Medicine of Guilin Medical University (No.Gui Xue Wei[2020]7).
文摘This study aims to investigate the impact of hepatocyte nuclear factor 1β(HNF1b)on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum(PAOA-flavone)-promoted small ubiquitin-related modifier(SUMO)modification in the atheroprotective efficacy of HNF1b.HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics,dual-luciferase reporter gene assay,and chromatin immunoprecipitation.HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages,leading to a depression in atherosclerotic plaque formation in low-density lipoprotein(LDL)receptor-deficient(LDLR−/−)mice.Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification.The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages.PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1(SAE1)expression and SAE1-catalyzed SUMOylation of the HNF1b protein,which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient(ApoE−/−)mice.Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration.In summary,HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis.This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated,SAE1-catalyzed SUMOylation of the HNF1b protein.
基金This research was funded by Natural Science Foundation of Guangdong Province(2018B030311012)Natural Science Foundation of China(82070811,81770826)+2 种基金Sci-Tech Research Development Program of Guangzhou City(202201020497)National Key R&D Program of China(2017YFA0105803)Key Area R&D Program of Guangdong Province(2019B020227003).
文摘Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug development based on glucokinase(GK)activation is an important strategy for lowering blood glucose.This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice.Materials and methods:Mice were fed with a high-fat diet(HFD)for 16 weeks to induce obesity,followed by a GK activator(GKA,AZD1656)or vehicle treatment by gavage for 4 weeks.The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests.Hepatic lipid accumulation was assessed by hematoxylin and eosin staining,Oil Red O staining,and transmission electron microscopy.The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis,with a mechanistic study in mouse livers in vivo and AML12 cells in vitro.Results:GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation.Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase(PERK)-unfolded protein response(UPR)pathway activations in GKA-treated HFD-fed mice.Inhibition of the ACC activity,which is an important protein in lipogenesis,attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro.Conclusions:GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression,which subsequently activated the hepatic PERK-UPR signaling pathway.
基金Sci-Tech Support Plan of Hubei Province (grant no. 2015BCA273)United fund for innovation and entrepreneurship of Ministry of education (201601031006)
文摘Objective:To evaluate the effect of high concentration of chlorogenic acid(CGA)on non-alcoholic fatty liver disease(NAFLD)in normal and oleic acid(OA)treated Hep G2 cells,as well as the underlying mechanism involved in the fat accumulation,oxidative stress and insulin resistance(IR)induced by CGA treatment.Methods:OA(0.5 mmol/L)induced hepatic steatosis was established in Hep G2 cells as an in vitro model of NAFLD.The normal and OA-treated Hep G2 cells were treated by CGA(0,0.5,1,and 2 mmol/L)for24 h,then cellular lipid droplets,reactive oxygen species(ROS),and glucose uptake were evaluated by Oil Red O staining and cellular biochemical assays,respectively.Signaling pathways involved in adipogenesis including SREBP-1c and PNPLA3,oxidative stress,and IR including CYP2E1 and CYP4A,were investigated by Western blot and RT-q PCR.Results:CGA(0.5,1,and 2 mmol/L)treatment increased the cellular lipid droplets and the expression of SREBP-1c and PNPLA3 in the tested cells.Additionally,2-NBDG uptake was significantly increased,whereas the cellular ROS and protein levels of CYP2E1 and CYP4A were significantly decreased in OA-treated cells.Conclusion:Our results suggest that high concentrations of CGA ameliorated OA-induced oxidative damage and IR likely by inhibiting the expression of CYP2E1 and CYP4A,and promoted lipid accumulation by inducing the expression of SREBP-1c and PNPLA3 in the tested cells.
基金This work was financially supported by the National Natural Science Foundation of China(Grant No.81770580)open funding from the Sichuan Provincial Key Laboratory of Radiation Oncology(Grant No.2020FSZLX-02).
文摘Background and Aims:Lipid accumulation is the major characteristic of non-alcoholic fatty liver disease,the prevalence of which continues to rise.We aimed to investigate the effects and mechanisms of icaritin on lipid accumulation.Methods:Cells were treated with icaritin at 0.7,2.2,6.7,or 20μM for 24 h.The effects on lipid accumulation in L02 and Huh-7 cells were detected by Bodipy and oil red O staining,respectively.Mitochondria biogenesis of L02 cells was detected by MitoTracker Orange staining.Glucose uptake and adenosine triphosphate content of 3T3-L1 adipocytes and C2C12 myotubes were detected.The expression levels of proteins in the adenosine 5′-monophosphate-activated protein kinase(AMPK)signaling pathway,biomarkers of autophagy,and mitochondria biogenesis were measured by western blotting.LC3 puncta were detected by immunofluorescence.Results:Icaritin significantly attenuated lipid accumulation in L02 and Huh-7 cells and boosted the mitochondria biogenesis of L02 cells.Icaritin enhanced glucose uptake,decreased adenosine triphosphate content,and activated the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes.Icaritin boosted autophagy and also enhanced the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts.However,icaritin decreased autophagy and promoted mitochondria biogenesis in 3T3-L1 adipocytes and C2C12 myotubes.Conclusions:Icaritin attenuates lipid accumulation by increasing energy expenditure and regulating autophagy by activating the AMPK pathway.
文摘This study compared the growth and lipid accumulation properties of two oleaginous microalgae, namely, Scenedesmus sp. LX1 and Chlorella sp. HQ, under different nutrient conditions. Both algal species obtained the highest biomass, lipid content and lipid yield under low-nutrient conditions (mBGll medium). The biomass, lipid content and lipid yield of Scenedesmus sp. LX1 were 0.42g·L^-1, 22.5% and 93.8mg·L^-1, respectively. These values were relatively higher than those of Chlorella sp. HQ (0.30g·L^-1, 17.1% and 51.3mg·L^-1, respectively). These algae were then cultivated in an SE medium that contained more nutrients; as a result, the biomass and lipid yield of Scenedesmus sp. LX1 reduced more significantly than those of Chlorella sp. HQ. Opposite results were observed in lipid and triacylglycerols (TAGs) contents. The cell sizes of both algal species under low-nutrient conditions were larger than those under high-nutrient conditions. Chlorella sp. HQ cells did not aggregate, but Scenedesmus sp. LX1 cells flocculated easily, particularly under low-nutrient conditions. In summary, low-nutrient conditions favour the growth and lipid production of both algae, but Scenedesmus sp. LX1 outperforms Chlorella sp. HQ.
文摘As significant differences in cellular physiology, metabolic potential and genetics occur among strains with morphological similarity, the screening of appropriate microalgae species for effective CO2 fixation and biodiesel production is extremely critical. In this study, ten strains of Chlorella were cultivated in municipal wastewater influent(MWI) and their tolerance for MWI, CO2 fixation efficiency and lipid productivity were assessed. The results showed that the biomass concentrations of four strains(Chlorella vulgaris, Chlorella64.01, Chlorella regularis var. minima and Chlorella sp.) were significantly higher than other strains. When the cultivation systems were aerated with 10% CO2, Chlorella sp. showed the highest CO2 fixation efficiency(35.51%), while the highest lipid accumulation(58.48%) was observed with C. vulgaris. Scanning electron microscopy images revealed that the cells of both Chlorella sp. and C. vulgaris kept their normal morphologies after 15 day batch culture.These findings indicated that Chlorella sp. and C. vulgaris have fairly good tolerance for MWI,and moreover, Chlorella sp. was appropriate for CO2 fixation while C. vulgaris represented the highest potential for producing biodiesel.