Polysaccharide-rich extract of Potentilla anserina ameliorates nonalcoholic fatty liver disease in free fatty acid-induced HepG2 cells and high-fat/sugar diet-fed mice

Potentilla anserina L.(PA)belongs to the Rosaceae family,is a common edible plant in the Qinghai-Tibet Plateau areas of China.This study elucidates the mechanism upon which crude polysaccharide of PA(PAP)on fat accumulation in HepG2 cells stimulated by oleic acid(OA)and high fat high sugar induced mice.The result revealed that PAP inhibited lipid accumulation in obese mice and ameliorated the degree of damage in OA-induced HepG2 cells.Specifically,compared to the control group,the TG and TC levels were decreased in cells and mice serum,the aspartate transaminase and alamine aminotransferase contents were declined in liver of obese mice by PAP treatment.The expressions of adipogenic genes of SREBP-1c,C/EBPα,PPARγ,and FAS were inhibited after PAP treatment.Moreover,PAP increased the mRNA levels of CPT-1 and PPARα,which were involved in fatty acid oxidation.The present results indicated the PAP could alleviate the damage of liver associated with obesity and PAP treatment might provide a dietary therapeutic option for the treatment of hyperlipidemia.

Comparative acetylome analysis reveals the potential mechanism of high fat diet function in allergic disease

Modern technological lifestyles promote allergic diseases,especially food allergies.The underlying molecular mechanisms remain to be uncovered.Protein acetylation is one of the most important post-translational modifications,and it is involved in regulating multiple body metabolic processes.This study aimed to clarify the effects of a high-fat diet(HFD)on allergy risk and the underlying mechanisms.Four-week-old male C57 BL/6 J mice were randomly divided into two groups and fed a normal fat diet(NFD)or HFD for 24 weeks.Then,serum lipids were measured,and skeletal muscle was collected for acetylome analysis.Compared with the findings in the NFD group,HFD-fed mice were obese and hyperlipidemic.Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups.Among these,eight acetylated proteins were upregulated in the HFD group.In addition,13 and 11 proteins were acetylated only in the HFD group and NFD group,respectively.These proteins were mainly involved in regulating energy metabolism and mitochondrial function.This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.

Negative effects of long-term feeding of high-grain diets to lactating goats on milk fat production and composition by regulating gene expression and DNA methylation in the mammary gland

Background： It is well known that feeding a high concentrate（HC） diet to lactating ruminants likely induces subacute ruminal acidosis（SARA） and leads to a decrease in milk fat production. However, the effects of feeding a HC diet for long periods on milk fatty acids composition and the mechanism behind the decline of milk fat still remains poorly understood. The aim of this study was to investigate the impact of feeding a HC diet to lactating dairy goats on milk fat yield and fatty acids composition with an emphasis on the mechanisms underlying the milk fat depression. Seventeen mid-lactating dairy goats were randomly allocated to three groups. The control treatment was fed a low-concentrate diet（35% concentrate, n = 5, LC） and there were two high-concentrate treatments（65% concentrate, HC）, one fed a high concentrate diet for a long period（19 wks, n = 7, HL）; one fed a high concentrate diet for a short period of time（4 wk, n = 5, HS）. Milk fat production and fatty acids profiles were measured. In order to investigate the mechanisms underlying the changes in milk fat production and composition,the gene expression involved in lipid metabolism and DNA methylation in the mammary gland were also analyzed.Results： Milk production was increased by feeding the HC diet in the HS and HL groups compared with the LC diet（P 〈 0.01）, while the percentage of milk fat was lower in the HL（P 〈 0.05） but not in the HS group. The total amount of saturated fatty acids（SFA） in the milk was not changed by feeding the HC diet, whereas the levels of unsaturated fatty acids（UFA） and monounsaturated fatty acids（MUFA） were markedly decreased in the HL group compared with the LC group（P 〈 0.05）. Among these fatty acids, the concentrations of C15：0（P 〈 0.01）, C17：0（P 〈 0.01）, C17：1（P 〈 0.01）, C18：1 n-9 c（P 〈 0.05）, C18：3 n-3 r（P 〈 0.01） and C20：0（P 〈 0.01） were markedly lower in the HL group, and the concentrations of C20：0（P 〈 0.05） and C18：3 n-3 r（P 〈 0.01） were lower in the HS group compared with the LC group. However, the concentrations of C18：2 n-6 c（P 〈 0.05） and C20：4 n-6（P 〈 0.05） in the milk fat were higher in the HS group. Real-time PCR results showed that the m RNA expression of the genes involved in milk fat production in the mammary gland was generally decreased in the HL and HS groups compared with the LC group. Among these genes, ACSL1, ACSS1 ＆ 2, ACACA, FAS, SCD, FADS2, and SREBP1 were downregulated in the mammary gland of the HL group（P 〈 0.05）, and the expressions of ACSS2, ACACA, and FADS2 m RNA were markedly decreased in the HS goats compared with the LC group（P 〈 0.05）. In contrast to the gene expression, the level of DNA methylation in the promoter regions of the ACACA and SCD genes was increased in the HL group compared with the LC group（P 〈 0.05）. The levels of ACSL1 protein expression and FAS enzyme activity were also decreased in the mammary gland of the HL compared with the LC group（P 〈 0.05）.Conclusions： Long-term feeding of a HC diet to lactating goats induced milk fat depression and FAs profile shift with lower MUFAs but higher SFAs. A general down-regulation of the gene expression involved in the milk fat production and a higher DNA methylation in the mammary gland may contribute to the decrease in milk fat production in goats fed a HC diet for long time periods.

Eating as a motivated behavior:modulatory effect of high fat diets on energy homeostasis,reward processing and neuroinflammation

Eating is a basic motivated behavior that provides fuel for the body and supports brain function.To ensure survival,the brain’s feeding circuits are tuned to monitor peripheral energy balance and promote food-seeking behavior when energy stores are low.The brain’s bias toward a positive energy state,which is necessary to ensure adequate nutrition during times of food scarcity,is evolutionarily conserved across mammalian species and is likely to drive overeating in the presence of a palatable,energy-dense diet.Animal models of diet-induced overeating have played a vital role in investigating how the drive to consume palatable food may override the homeostatic processes that serve to maintain energy balance.These animal models have provided valuable insights into the neurobiological mechanisms underlying homeostatic and non-homeostatic eating,motivation and food reward,and the development of obesity and related comorbidities.Here,we provide a brief review of this literature and discuss how diet-induced inflammation in the central nervous system impacts the neural control of food intake and regulation of body weight.The connection between diet and the immune system provides an exciting new direction for the study of ingestive behavior and the pathophysiology of obesity.

Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.

Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases

Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.

High fat diet feeding results in gender specific steatohepatitis and inflammasome activation

AIM: To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge.

High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.

Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats

AIM: To investigate the effect of Platycodon grandi- florum extract (PGE) on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats. METHODS: PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03 ± 7.61 g were divided into four groups: the control groups that fed an experimental diet alone (C and H group) and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight (C + PGE and H + PGE group, respectively) for 7 wk. Plasma total cholesterol (TC) and triglycerol (TG) concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein (FABP) mRNA expression was analyzed by northern blot analysis. RESULTS: PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE signifi cantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue. CONCLUSION: PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat diet.From these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.

The effects of the extract of oolong tea and its metabolites from Andraca theae in high fat diet induced obese Wistar rat

Obesity is a critical health issue worldwide.For a long time,the concept of drinking tea for health and pleasure is widely accepted.The strain of Andraca theae lives on the tea leaf and the bioactivity of its metabolites in the feces is unknown yet.Thus,the objective of this study was to investigate whether the extract of tea(Taiwan Tea Experiment Station No.12(TE))and its metabolites from Andraca theae(TME)could prevent obesity in the high fat diet-induced obese rats.Our results showed that TE had higher concentrations of epigallocatechin gallate(EGCG)and caffeine than that from TME.TE significantly decreased abdominal adipose tissue,especially epididymal fat via increasing preadipocyte factor 1(Pref-1),SRY(sex determining region Y)-box 9(SOX-9)and decreasing peroxisome proliferator-activated receptorγ(PPARγ),CCAAT/enhancer binding protein(C/EBP)β,C/EBPαand C/EBPβprotein expression.Taken together,these results suggest that the content of tea polyphenols in TE play an important role for alleviating abdominal fat.

Effects of Siraitia grosvenorii extracts on high fat diet-induced obese mice:a comparison with artificial sweetener aspartame

Long-term artificial sweetener intake is linked to increased risk of obesity. In the present study, supplement of natural sweetener from Siraitia grosvenorii(SG)(or Momordica grosvenorii) fruit, compared with the artificial sweetener aspartame(ASM), was evaluated for anti-obesity effects on mice fed with high fat diet(HFD). We found that, in contrary to ASM, SG extracts prevented body weight gain, the insulin resistance and fat mass accumulation in HFD mice. SG extracts treatment inhibited the infiltration of inflammatory macrophages and lowered the levels of the fat inflammatory cytokines(leptin, macrophage chemoattractant protein 1(MCP-1) and tumor necrosis factor-α(TNF-α)) in adipose tissues. In addition, SG extracts supplement counteracted the remodeling of gut microbiota resulted from HFD. However, ASM supplement aggravated the HFD-induced obese performances, fat inflammation and dysregulation of gut microbiota. Taken together, our results indicate that supplement of SG extracts may represent a promising alternation of artificial sweeteners in preventing metabolic diseases.

Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism

BACKGROUND Studies have shown that a high-fat diet(HFD) can alter gut microbiota(GM)homeostasis and participate in lipid metabolism disorders associated with obesity.Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract(Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases.AIM To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism.METHODS Obesity was induced in rats with an HFD for 7 wk, and Sal(0.675 g/1.35 g/2.70g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors(cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNAbased microbiota analysis and untargeted lipidomic analysis(LC-MS/MS),respectively.RESULTS Sal treatment markedly reduced weight, body fat index, serum triglycerides(TG), total cholesterol(TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein(HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as c AMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs(TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs(DG14:0/22:6, DG22:6/22:6), CL(18:2/18:1/18:1/20:0), and increased ceramides(Cers;Cer d16:0/21:0, Cer d16:1/24:1),(O-acyl)-ω-hydroxy fatty acids(OAHFAs;OAHFA18:0/14:0) in the feces of rats. Spearman’s correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite.CONCLUSION Sal has an anti-obesity effect by regulating the GM and lipid metabolism.

Comparative study on the difference of obesity model induced by two kinds of high fat diet in Sprague-Dawley rats

Objective: To explore the differences of obese Sprague-Dawley(SD)rats model induced by lard oil high-fat(HF)diet or purified HF diet. Methods: SD weanling rats were randomly divided into three groups: D1 group,where rats were fed by lard oil HF diet;D2 group,where rats were fed by purified HF diet;C group,where rats were fed on chow. After 12 weeks,diet-induced obesity rat(stop 33% based on weight)were selected for further study,and the rest rats from group D1 and D2 were excluded. The food intake and weight were weighted daily and weekly,respectively. The subcutaneous,visceral and total fat contents of rats was measured by 256-row CT scan and the Lee index was calculated accordingly. The kidney,liver,testis,spleen and heart were weighted respectively. Serum leptin and insulin levels were quantified. The pathology in liver and adipose tissues were analyzed by HE staining. Oral glucose tolerance test(OGTT)was used to compare the glucose tolerance ability. Serum total cholestero(lT-CHO),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),triglyceride(TG)and inflammatory cytokines IL-6,TNF-α were detected as well. Results: After 12 weeks,the body weight,subcutaneous fat,visceral fat,total fat mass,wet weight of liver,kidney and heart,area under blood glucose curve and the levels of serum insulin,leptin,T-CHO,LDL-C,TG,IL-6 and TNF-α in group D2 were significantly increased compared to those of group C and group D1. HDL-C of group D2 was markedly lower than that in group C(P<0. 05). The visceral fat,total fat content and HDL-C in group D1 were significantly different from those of group C(P<0. 05). Steatosis and enlarged adipocyte were found in the livers of rats in group D1 and D2,and the lesions were more significant in group D2. Conclusion: Purified HF diet was more effective in inducing metabolic abnormalities,steatosis,peripheral chronic inflammation in obese SD rat models. But lard oil HF diet was more economical when only inducing visceral steatosis was required.

Conditioned Place Preference Deficits in Adulthood Following High Fat and High Sugar Diet Intake in Pre- and Periadolescence: A Test of the Specificity Hypothesis

Obesity is linked to poorer cognitive performance, both of which may result from eating high-fat foods during development. In the present study, pre-and periadolescent (postnatal days 21 to 40) male rats were fed high fat (HF), high sugar (HS), or rodent chow (Chow) diets. After conditioning for 16 days with either Cheetos? (high-fat) or Froot Loops? (high-sugar) unconditioned stimuli (US) on one side of a conditioned place preference (CPP) apparatus, rats were tested on postnatal day 61 for a place preference. Chow rats preferred the US-paired side, but HF rats showed no preference. HS rats preferred the side paired with Cheetos? but not with Froot Loops?. In spite of these deficits, object recognition, a nonassociative learning task, was not impaired. These results show mixed support for the specificity hypothesis, which predicts that CPP deficits will be nutrient-specific. The results show for the first time that eating a HS diet leads to a nutrient-specific CPP deficit (for HS foods), whereas eating a HF diet leads to a general CPP deficit (for HS and HF foods).

Effects of Mogroside V on Glucose and Lipid Metabolism in High Fat Diet Mice

[Objectives]To explore the effects and mechanism of mogroside V(MV)on glucose and lipid metabolism in high-fat diet(HFD)mice.[Methods]The experiment fed mice with high-fat diet for 8 weeks,and 40 mice with successful modeling were randomly divided into normal group,model group,and MV dose group(100,200 mg/kg),with 10 mice in each group.From the ninth week,the MV dose group was given intragastric administration,and the normal group and the model group were given an equal volume of distilled water by intragastric administration for 6 weeks,then killed and blood samples and livers were collected.Serum triglycerides(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),Advanced glycation end products(AGE-P)-peptides(AGE-P)and glycosylated hemoglobin(HbA1c)content,and TG and hepatic glycogen content in liver were detected by biochemical method.Fasting blood glucose(FBG)was measured by glucose oxidase method.The fasting serum insulin(FINS)content was detected by enzyme-linked immunosorbent assay(ELISA),and the insulin resistance index(HOMA-IR)was calculated.Oil red O staining was used to observe the fat deposition in liver tissue.[Results]MV(100,200 mg/kg)dose groups could significantly down-regulate the contents of TC,TG,LDL-C,FBG,FINS,AGE-P and HbA1c and HOMA-IR,and up-regulate HDL-C and hepatic glycogen content and reduce the fat deposits.[Conclusions]The mechanism of MV regulating glucose and lipid metabolism in mice may be related to the regulation of insulin resistance.

Palmitoleic acid on top of HFD ameliorates insulin resistance independent of diacylglycerols and alters gut microbiota in C57BL/6J mice

With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.

mi R-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1

AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.

Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver disease

BACKGROUND:Non-alcoholic fatty liver disease(NAFLD)is one of the most frequent causes of liver diseases,with markedly increased prevalence.However,its mechanisms are not clear.The present study was undertaken to illustrate the role of caveolin-1(cav1)and the scavenger receptor class B type 1(SR-B1)in NAFLD.METHODS:Adult male C57BL/6 mice were fed with a normal diet or high fat and cholesterol(HFC)diet for 14 weeks.The mice were sacrificed to collect plasma and harvest the liver;their plasma lipid concentration was measured.Hepatic cav1and SR-B1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.In order to study cav1 and SR-B1distribution and change in hepatocytes,immunohistochemical analysis was performed.RESULTS:HFC diet increased plasma lipids,induced NAFLD and increased the liver/body weight ratio.Compared to the control mice(n=6),the mRNA and protein levels of cav1 and SR-B1 in liver tissue of the NAFLD mice(n=12)increased significantly(cav1 mRNA:1.536±0.226 vs 0.980±0.272,P【0.05;protein:0.643±0.240 vs 0.100±0.130,P【0.01;SR-B1 mRNA:1.377±0.125 vs 0.956±0.151,P【0.01;protein:2.156±0.507vs 0.211±0.211,P【0.01).Furthermore,both cav1 and SR-B1immunoreactivity increased and their distribution was also changed,mainly in the plasma membrane of hepatocytes,cytoplasm and membrane of lipid droplets and around.CONCLUSION:NAFLD is associated with increased concentration of plasma lipids and upregulation of hepatic cav1 and SR-B1 gene and protein expressions,which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.

Papaya improves non-alcoholic fatty liver disease in obese rats by attenuating oxidative stress,inflammation and lipogenic gene expression

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a global health issue that is correlated with obesity and oxidative stress.AIM To evaluate the anti-NAFLD effect of papaya in high fat diet induced obesity in rats.METHODS Four-week-old male Sprague-Dawley rats were divided into four groups after 1 wk of acclimatization:Group 1 was the rats fed a normal diet(C);group 2 was the rats fed a high fat diet(HFD);group 3 was the rats fed a HFD with 0.5 mL of papaya juice/100 g body weight(HFL),and group 4 was the rats fed a HFD with 1 mL of papaya juice/100 g body weight(HFH)for 12 wk.At the end of the treatment,blood and tissue samples were collected for biochemical analyses and histological assessment.RESULTS The results of the HFH group showed significantly reduced body weight(HFH vs HFD,P<0.01),decreased NAFLD score(HFH vs HFD,P<0.05),and reduced hepatic total cholesterol(HFL vs HFD,P<0.01;HFH vs HFD,P<0.001),hepatic triglyceride(HFH vs HFD,P<0.05),malondialdehyde(HFL,HFH vs HFD,P<0.001),tumour necrosis factor-α(HFH vs HFD,P<0.05)and interleukin-6(HFH vs HFD,P<0.05)when compared to the HFD group.However,the liver weight showed no significant difference among the groups.The activities of catalase and superoxide dismutase significantly increased in HFH when compared with the HFD group(P<0.05 and P<0.001,respectively).The suppression of transcriptional factors of hepatic lipogenesis,including sterol regulatory elementbinding protein 1c and fatty acid synthase,were observed in the papaya treated group(HFH vs HFD,P<0.05).These beneficial effects of papaya against HFDinduced NAFLD are through lowering hepatic lipid accumulation,suppressing the lipogenic pathway,improving the balance of antioxidant status,and lowering systemic inflammation.CONCLUSION These current results provide experimental-based evidence suggesting papaya is an efficacious medicinal fruit for use in the prevention or treatment of NAFLD.

Rosiglitazone reduces fatty acid translocase and increases AMPK in skeletal muscle in aged rats： a possible mechanism to prevent high-fat-induced insulin resistance

Background As an agonist of peroxisome proliferator-activated receptor-gamma （PPARy）, rosiglitazone can prevent acute fatty acid-induced insulin resistance in rats, however, the precise mechanisms by which rosiglitazone alleviates insulin resistance induced by high-fat diet need to be further investigated.Methods Wistar rats aged 23-24 weeks were divided into three groups： （1） aged control group （OC）, （2） high-fat diet （HF） group and （3） high-fat diet plus rosiglitazone maleate tablets （HF＋Rosi） treatment group （n=20 in each group）. Insulin sensitivity was evaluated by conscious hyperinsulinemic-euglycemic clamp technique. mRNA levels of fatty acid translocase （FAT/CD36）, AMP-activated protein kinase α1 （AMPKα1）, AMPKα2 and acetyl CoA carboxylase （ACC） of rat skeletal muscle were determined using real-time PCR, while muscle camitine palmitoyltransferase-1 （CPT-1β） was determined using semi-quantitative PCR. Protein expression levels of FAT/CD36, AMPK phosphorylation （reflecting AMPK activity）, P-ACC （inversely related with ACC activity） and muscle CPT-1M in rat skeletal muscles were measured using Western blotting.Results Aged rats fed by diet rich in fat for more than 8 weeks led to significant increases of plasma lipids, skeletal muscle intramuscular triglyceride and long-chain fatty acyl-CoA （LCACoA） compared to aged rats fed by normal chow diet （OC） （P 〈0.05）, which might correlate with the lower （reduced by 42.4%） whole body insulin sensitivity in HF rats. FAT/CD36 protein concentrations and mRNA levels increased in untreated HF aged rats （P 〈0.01） and high-fat diet induced a significant decrease in P-AMPK, P-ACC, CPT-1M protein concentrations and AMPKα2 and CPT-1β mRNA levels in rat skeletal muscles （P 〈0.05）. No change in AMPKα1 mRNA levels was observed in the HF group.Conclusion High-fat diet in aged rats results in a lipid accumulation and subsequent insulin resistance, while rosiglitazone can alleviate the insulin resistance by reducing fatty acid uptake as well as enhancing lipometabolism.