Secreted Frizzled-Related Protein 5 Mediates Wnt5a Expression in Microcystin-Leucine-Arginine-Induced Liver Lipid Metabolism Disorder in Mice

Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Characteristics of glucose and lipid metabolism and the interaction between gut microbiota and colonic mucosal immunity in pigs during cold exposure

Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.

Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance

BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the relationship between vitamin D and IR in T2DM patients requires further investigation.AIM To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM.METHODS Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed.Based on the diagnostic criteria of IR,the patients were divided into a resistance group(n=100)and a non-resistance group(n=62).Subsequently,patients in the resistance group were subdivided to a conventional group(n=44)or a joint group(n=56)according to the treatment regimens.Logistic regression was carried out to analyze the risk factors of IR in T2DM patients.The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment.RESULTS Notable differences were observed in age and body mass index(BMI)between the resistance group and the non-resistance group(both P<0.05).The resistance group exhibited a lower 25-hydroxyvitamin D_(3)(25(OH)D_(3))level,as well as notably higher levels of 2-h postprandial blood glucose(2hPG),fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)than the non-resistance group(all P<0.0001).Additionally,the resistance group demonstrated a higher triglyceride(TG)level but a lower high-density lipoprotein-cholesterol(HDL-C)level than the non-resistance group(all P<0.0001).The BMI,TG,HDL-C,25(OH)D_(3),2hPG,and HbA1c were found to be risk factors of IR.Moreover,the posttreatment changes in levels of 25(OH)D_(3),2hPG,FBG and HbA1c,as well as TG,total cholesterol,and HDL-C in the joint group were more significant than those in the conventional group(all P<0.05).CONCLUSION Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the noninsulin resistant group.Logistic regression analysis revealed that 25(OH)D_(3)is an independent risk factor influencing IR.Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.

Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.

Decabromodiphenyl ether causes insulin resistance and glucose and lipid metabolism disorders in mice

BACKGROUND Decabromodiphenyl ether(BDE-209)is the most commonly used brominated flame retardant.Recently,BDE-209 has been suspected of being an environmental risk factor for metabolic diseases such as obesity,insulin resistance(IR),type 2 diabetes mellitus,and hypertension.AIM To investigate the effects of BDE-209 on IR and glucose and lipid metabolism in C57BL/6 mice.METHODS Adult male C57BL/6 mice were randomly divided into high,medium-high,medium,medium-low,and low dose BDE-209 groups,and a control group(n=6 per group),which received 1000,800,600,450,300,and 0 mg/kg BDE-209,respectively.After BDE-209 exposure for 60 d,the mice were fasted overnight,and then sacrificed to obtain tissues.An automatic biochemical analyzer was used to detect serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C);enzymelinked immunosorbent assay kits were used to detect fasting serum insulin(FINS),leptin(LEP),and adiponectin(Adp)levels;a blood glucose meter was used to detect fasting blood glucose(FBG).Morphological changes of the liver were observed by hematoxylin and eosin staining.Real-time quantitative polymerase chain reaction and Western blot were used to determine the messenger ribonucleic acid(mRNA)and protein levels,respectively,of LEP,Adp,and peroxisome proliferators activated receptor-γ(PPARγ)in mouse liver and adipose tissues.RESULTS There was a statistically significant difference in the weight of mice in each group after 45 and 60 d of exposure(P<0.05).After 60 d of exposure,the weight of liver and adipose tissues in the exposure groups were greater than that of the control group(P<0.05).The liver tissue structure was disordered and the liver tissues were accompanied by local inflammatory cell infiltration in the high,mediumhigh,and medium dose BDE-209 groups.The levels of FINS,insulin sensitivity index,Adp,and HDL-C were decreased in the BDE-209 group compared with the control group,as were the mRNA and protein levels of Adp in liver and adipose tissues(P<0.05).Serum level of FBG and LEP were higher in the BDE-209 group than in controls.TC,TG,and LDL-C levels as well as the mRNA and protein expression of LEP and PPARγin liver and adipose tissues were higher than those in the control group(P<0.05).Homeostatic assessment model of IR was higher in the medium and medium-low dose BDE-209 groups(P<0.05).CONCLUSION BDE-209 increases the body weight,fat and liver tissue weight,TC,TG,and LDLC,reduces HDL-C,and causes IR in mice,which may be related to activating the PPARγreceptor.

Association between polymorphism of MC4R rs489693 gene and disorder of glucose and lipid metabolism in schizophrenia patients treated with olanzapine

Objective:To investigate the effect of Melanocortin four receptor,MC4R rs489693 polymorphism on glucose and Lipid metabolism in schizophrenia patients treated with Olanzapine for 12 weeks.Methods:171 patients with schizophrenia were divided into AA Group(N=12),AC group(N=59)and CC Group(N=100)according to the polymorphism of MC4R gene at 489693 locus detected by DNA sequencing.Blood Glucose and lipid levels were measured before and 12 weeks after treatment,the differences of variables among the 3 groups were compared,and the incidence of glucose and lipid abnormalities after treatment was statistically analyzed.Results:After 12 weeks of treatment,the net increase of blood glucose in AA group was greater than that in CC group(P<0.05),and the net increase of cholesterol and triglyceride in AA group was greater than that in AC group and CC group(all P<0.05),and the incidence of Blood Glucose and at least one dyslipidemia in AA Group was higher than that in AC and CC group(all P<0.01).Conclusion:The rs489693 gene polymorphism of MC4R gene is related to the disorder of glucose and lipid metabolism in schizophrenia treated with olanzapine.

Short-term night lighting disrupts lipid and glucose metabolism in Zebra Finches:Implication for urban stopover birds

Night lighting has been shown to affect wild animals.To date,the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear.Using model bird species Zebra Finch(Taeniopygia guttata),we investigated the effects of short-term night lighting on liver transcriptome,blood glucose,triglyceride,and thyroxine(T4 and T3)levels in birds exposed to two different night lighting duration periods(three days and six days).After three days of night lighting exposure,the expression of genes involved in fat synthesis in the liver was upregulated while the expression of genes involved in fatty acid oxidation and triglyceride decomposition was downregulated.There was also a reduction in blood triglyceride,glucose,and T3 concentrations.However,after six days of night lighting,the expression of genes associated with fatty acid decomposition and hyperglycemia in the liver was upregulated,while the expression of genes involved in fat synthesis was downregulated.Simultaneously,blood glucose levels and T3 concentration increased.These findings indicate that short-term exposure to night lighting can disrupt the lipid and glucose metabolism of small passerine birds,and longer stopovers in urban area with intense night lighting may cause birds to consume more lipid energy.

Research progress on adaptive modifications of the gut microflora and regulation of host glucose and lipid metabolism by cold stimulation

The gut microflora is a combination of all microbes in intestine and their microenvironment,and its change can sensitively reflect the relevant response of the body to external environment and remarkably affect body's metabolism as well.Recent studies have found that cold exposure affects the body's gut microflora,which can lead to changes in the body's metabolism of glucose and lipid.This review summarizes recent research on the effects of cold exposure on gut microbes and metabolism of glucose and lipid,aiming to provide some new ideas on the approaches and measures for the prevention and treatment of diabetes and obesity.

NLRP3 Inflammasome in Relation to Glucose and Lipid Metabolism, and Insulin Resistance in Diabetes and Pre-Diabetes

Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with abnormal blood glucose divided into the pre-diabetes mellitus (PDM) group (N = 46) and the type 2 diabetes mellitus (T2DM) group (N = 54). 20 normoglycemic subjects (NG, N = 20) were selected as a control group. The serum levels of glucose and lipid metabolism, IR, and the expression of NLRP3, ASC and Caspase-1 were measured. Besides, the correlations of NLRP3 inflammasome with glucose and lipid metabolism, and IR were analyzed. Results: Compared with the NG group, the levels of NLRP3, ASC, Caspase-1, FBG, HbA1C, TG, LDL-C, FINs, and HOMA-IR were higher (P β were lower (P P β were seen (P P β. Regression analysis further showed that blood glucose related indexes, FINs, and NLRP3 have made a decisive contribution to IR. Conclusions: Collectively, this evidence suggested that NLRP3 is closely related to glucose and lipid metabolism, and IR, and activated in PDM and T2DM.

Effects of over-expressing resistin on glucose and lipid metabolism in mice

Resistin,a newly discovered peptide hormone mainly secreted by adipose tissues,is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However,some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans,no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study,we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection,serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice,both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control,whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore,lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.

Short-chain fatty acids can improve lipid and glucose metabolism independently of the pig gut microbiota

Background:Previous studies have shown that exogenous short-chain fatty acids(SCFAs)introduction attenuated the body fat deposition in conventional mice and pigs.However,limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota.This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free(GF)pig model.Methods:Twelve hysterectomy-derived newborn pigs were reared in six sterile isolators.All pigs were hand-fed with sterile milk powder for 21 d,then the sterile feed was introduced to pigs for another 21 d.In the second 21-d period,six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group,while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture(acetic,propionic,and butyric acids,45,15,and 11 mmol/L,respectively)per day and regarded as FA group.Results:Orally administrated with SCFAs tended to increase the adiponectin concentration in serum,enhance the CPT-1 activity in longissimus dorsi,and upregulate the ANGPTL4 mRNA expression level in colon(P<0.10).Meanwhile,the mRNA abundances of ACC,FAS,and SREBP-1C in liver and CD36 in longissimus dorsi of the FA group were decreased(P<0.05)compared with those in the GF group.Besides,the mRNA expression of PGC-1αin liver and LPL in longissimus dorsi tended to(P<0.10)upregulate and downregulate respectively in the FA group.Moreover,oral administration of SCFAs tended to increase the protein level of GPR43(P<0.10)and decrease the protein level of ACC(P<0.10)in liver.Also,oral administration of SCFAs upregulated the p-AMPK/AMPK ratio and the mRNA expressions of GLUT-2 and GYS2 in liver(P<0.05).In addition,the metabolic pathway associated with the biosynthesis of unsaturated fatty acids was most significantly promoted(P<0.05)by oral administration of SCFAs.Conclusions:Exogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the glucose control in the pig model,which occurred independently of the gut microbiota.

Effect of astragaloside Ⅳ on lipid and glucose metabolism in acute myocardial infarction through PPARγ pathway

OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.

Sucrose-free hawthorn leathers formulated with fructooligosaccharides and xylooligosaccharides ameliorate high-fat diet induced inflammation, glucose and lipid metabolism in liver of mice

High sucrose content in traditional hawthorn leathers limits the potential consumption, particularly for elders and diabetics. In this study, sucrose-free hawthorn leathers were formulated with 75% fructooligosaccharides(FOS) and 25% xylooligosaccharides(XOS)(HLF75), which exhibited comparable morphology and sensory properties to the traditional ones. Then, the anti-obesity activity of HLF75 was investigated using high-fat diet(HFD) fed C57BL/6J mice. Comparing with traditional hawthorn leathers, HLF75 supplementation in HFD significantly decreased the levels of blood glucose and serum lipid. The histomorphologies of liver and subcutaneous fat tissues were ameliorated by HLF75, as well as the down-regulated m RNA expression levels of IL-1β, Nos2 and Cox-2 in the liver. M oreover, the protein levels of M y D88 and NF-κB in the liver were suppressed by HLF75 treatment with decreased F4/80-positive macrophage number. Ho wever, the expression levels of PI3K, phosphorylated-AKT(Thr308), and phosphorylated-m TOR(Ser2448) proteins related to glucose metabolism were increased in the liver. Moreover, fat synthesis-related gene expression in HLF75-fed mice was suppressed while expressions of lipolysis genes were improved. Thus, HLF75 supplementation alleviated HFD-induced obesity through the alleviation of inflammation and restoration of the disturbed glucose and lipid metabolism. Functional oligosaccharides could be effective sucrose substitutes in hawthorn leathers and enable their potential utilization as functional foods.

Proteomic analysis of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention

Objective:To investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers.Methods:Seventy-one subjects were enrolled in the study.We assessed blood glucose,blood lipids,body mass index(BMI),and phlegm-dampness pattern,which was confirmed by a traditional Chinese medicine clinician.Of the participants,we included healthy participants with normal weight(NW,n=23),overweight/obese participants with normal metabolism(ONM,n=19),overweight/obese participants with pre-diabetes(OPD,n=12),and overweight/obese participants with marginally-elevated blood lipids(OML,n=17).Among them,the ONM,OPD,and OML groups were diagnosed with phlegmdampness pattern.The data-independent acquisition(DIA)method was first used to analyze the plasma protein expression of each group,and the relevant differential proteins of each group were screened.The co-expressed proteins were evaluated by Venn analysis.The pathway analyses of the differential proteins were analyzed using Ingenuity Pathway Analysis(IPA)software.Parallel reaction monitoring(PRM)was used to verify the differential and common proteins in each group.Results:After comparing ONM,OPD,and OML groups with NW group,we identified the differentially expressed proteins(DEPs).Next,we determined the DEPs among OPD,OML,and ONM groups.Using Venn analysis of the DEPs in each group,24 co-expressed proteins were screened.Two co-expressed proteins were verified by PRM.IPA analysis showed that pathways including LXR/RXR activation,acute phase response signaling,and FXR/RXR activation were common to all three groups of phlegmdamp overweight/obesity participants.However,the activation or inhibition of these pathways was different among the three groups.Conclusion:Participants with overweight/obesity have similar proteomic characteristics,though each type shows specific proteomic characteristics.Two co-expressed proteins,VTN and ORM1,are potential biomarkers for glucose and lipid metabolism diseases with overweight/obesity caused by phlegmdampness retention.

Effect of clozapine on the serum total bile acid, glucose and lipid metabolism in patients with schizophrenia

Objective:To observe the effect of clozapine on the serum total bile acid (TBA), glucose and lipid metabolism in patients with schizophrenia.Methods:A total of 80 patients with first-episode schizophrenia who were admitted in our hospital from January, 2015 to January, 2016 were included in the study and randomized into the observation group and the control group with 40 cases in each group. The patients in the observation group were given clozapine, while the patients in the control group were given risperidone. The serum TBA, T-Bil, D-Bil, I-Bil, glucose and lipid metabolism before and after treatment in the two groups were compared. Results:The comparison of TBA before and after treatment between the two groups was not statistically significant (P>0.05). T-Bil, D-Bil, and I-Bil after treatment were significantly reduced when compared with before treatment (P<0.05), but the comparison between the two groups was not statistically significant (P>0.05). BMI, waistline, hipline, and waist-hip ratio after treatment in the two groups were significantly elevated when compared with before treatment (P<0.05), and BMI, waistline, hipline, and waist-hip ratio after treatment in the observation group were significantly higher than those in the control group (P<0.05). The comparison of FBS, TC, TG, HDL-C, and LDL-C levels before treatment between the two groups was not statistically significant (P>0.05). FBS, TC, TG, and LDL-C levels 12 months after treatment were significantly elevated when compared with before treatment (P<0.05), but HDL-C was significantly reduced when compared with before treatment (P<0.05). FBS, TC, TG, and LDL-C levels 12 months after treatment in the observation group were significantly higher than those in the control group (P<0.05), but HDL-C was significantly lower than that in the control group (P<0.05).Conclusions:Clozapine has no obvious effect on TBA in patients with schizophrenia. Both of the two medications can produce effects on the glucose and lipid metabolism, but the effect by clozapine is more obvious;therefore, it should be paid attention in the clinical application.

Effect of DPP-4 inhibitor combined with metformin on glucose and lipid metabolism and micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome

Objective: To study the effect of DPP-4 inhibitor combined with metformin on glucose and lipid metabolism and micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome. Methods: A total of 60 patients with type 2 diabetes mellitus complicated by metabolic syndrome who were treated in the hospital between February 2015 and December 2016 were divided into control group (n=30) and observation group (n=30) according to the random number table method. Control group received metformin therapy alone, observation group received DPP-4 inhibitor combined with metformin therapy, and the differences in levels of glucose and lipid metabolism indexes and inflammatory factors were compared between the two groups of patients before and after treatment. Results: Before treatment, the differences in glucose and lipid metabolism index levels in peripheral blood as well as inflammatory factor contents in serum were not statistically significant between the two groups. After treatment, the levels of glucose metabolism indexes FPG, FPI and HOMA-IR as well as lipid metabolism indexes TG and TC in peripheral blood of observation group were lower than those of control group while HDL-C level was higher than that of control group;the contents of inflammatory factors IL-6, CRP and TNF-α in serum were lower than those of control group. Conclusion: DPP-4 inhibitor combined with metformin therapy is more effective in controlling the glucose and lipid metabolism process and inhibiting the micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome.

Chlorogenic acid modulates glucose and lipid metabolisms via AMPK activation in HepG2 cells and shows its anti-hyperglycemic effect on streptozocin-induced diabetic mice

Objective:In this study,we focus on the hypoglycemic effects of chlorogenic acid(CGA)in vitro and in vivo and its mechanism base on regulate glucose and lipid metabolism via AMPK activation.Methods:The cytotoxicity,glucose consumption and intracellular triglyceride assay were been detected by commercial kits.The western blots were used to detection the associated protein levels after CGA treatment,and the inhibiter blocking experiments were also be done.In vivo experiment,the fasting blood-glucose,lipid metabolism,liver function,insulin resistance,glucose tolerance,and pathological change were assessed on streptozocin induced diabetic mice.Results:We found that CGA exhibited no cytotoxicity at concentrations of 100μM,it caused a significant increasing of glucose consumption and reducing of the PA-BSA induced intracellular TG level on HepG2 cells at 50μM and 100μM treatment,CGA exhibited up-regulating the level of p-AMPK(Thr172)and p-ACC(Ser79)in dose-dependent manners in vitro and in vivo.The stimulating activities of CGA on AMPK were completely blocked by compound c(CC)on HepG2 cells.And the efficacies of CGA on glucose consumption and intracellular TG accumulation were also completely blocked by CC pretreatment.The CGA also exhibited potent anti-diabetic effects with hypoglycemic activity,improve insulin resistance and glucose tolerance,regulate glucose and lipid metabolism and protect the liver function in vivo.Conclusion:Our results suggested that CGA can regulate glucose and lipid metabolism by AMPK activation,and exhibit potent anti-hyperglycemic effect in streptozocin induced diabetes mice,and may be used as a potential effective anti-diabetes drug.

Global research trends and prospects of cellular metabolism in colorectal cancer

BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

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.