OBJECTIVES: Recent evidence suggests that the gut may be a primary site of metformin action. However, studies on the effects of metformin on gut microbiota remain limited, and its impact on gut microbial metabolites such as short-/medium-chain fatty acids is unclear. This study aims to investigate the effects of metformin on gut microbiota, short-/medium-chain fatty acids, and associated metabolic benefits in high-fat diet rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: 1) Normal diet group (ND group), fed standard chow; 2) high-fat diet group (HFD group), fed a high-fat diet; 3) high-fat diet + metformin treatment group (HFD+Met group), fed a high-fat diet for 8 weeks, followed by daily intragastric administration of metformin solution (150 mg/kg body weight) starting in week 9. At the end of the experiment, all rats were sacrificed, and serum, liver, and colonic contents were collected for assessment of glucose and lipid metabolism, liver pathology, gut microbiota composition, and the concentrations of short-/medium-chain fatty acids. RESULTS: Metformin significantly improved HFD-induced glucose and lipid metabolic disorders and liver injury. Compared with the HFD group, the HFD+Met group showed reduced abundance of Blautia, Romboutsia, Bilophila, and Bacteroides, while Lactobacillus abundance significantly increased (all P<0.05). Colonic contents of butyric acid, 2-methyl butyric acid, valeric acid, octanoic acid, and lauric acid were significantly elevated (all P<0.05), whereas acetic acid, isoheptanoic acid, and nonanoic acid levels were significantly decreased (all P<0.05). Spearman correlation analysis revealed that Lactobacillus abundance was negatively correlated with body weight gain and insulin resistance, while butyrate and valerate levels were negatively correlated with insulin resistance and liver injury (all P<0.05). CONCLUSIONS Metformin significantly increases the abundance of beneficial bacteria such as Lactobacillus and promotes the production of short-/medium-chain fatty acids including butyric, valeric, and lauric acid in the colonic contents of HFD rats, suggesting that metformin may regulate host metabolism through modulation of the gut microbiota.
Animals ; Metformin/pharmacology* ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects* ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Fatty Acids, Volatile/metabolism* ; Fatty Acids/metabolism*

Objective To observe the effects of constant light exposure on the obesity in high fat diet rats. Methods Thirty-two male SD rats were randomly divided into four groups:rats on a normal chow exposed to standard light-dark cycle ( group A) , rats on a normal chow exposed to constant light ( group B) , rats on a high fat diet exposed to standard light-dark cycle ( group C) , and rats on a high fat diet exposed to constant light ( group D) . Body weights and food intakes were recorded weekly throughout the 12-week study. Body weight, fat mass, visceral adipose tissue weight, intraperitoneal glucose tolerance test ( IPGTT) results, insulin resistance parameters, serum lipids and levels of interleukin 6 (IL-6), tumor necrosis factor-α(TNF-α) were compared among groups. Epididymal adipose tissues mRNA expression of circadian clock genes, i. e. clock, bmal1, rorα, rev-erbα, cry1, per1, and per2 were analyzed by realtime PCR. Results From the 9th week, body weights of rats in group D were significantly higher than those in group C (all P<0. 05). At the 12th week, area under curve of IPGTT (AUC-IPGTT) in groups B, C, and D were significantly higher than that in group A. AUC-IPGTT in group D was significantly higher than that in group C (all P<0.05). Compared with group C,asignificant increase in fat mass,visceral adipose tissue weight,homeostasis model assessment for insulin resistance, serum cholesterol, TNF-α levels were observed in group D ( all P<0. 05). And a significant decrease in quantitative insulin sensitivity check index ( QUICKI) and high density lipoprotein-cholesterol were observed in group D in comparison with group C (both P<0. 05). Circadian clock genes (clock, rorα, rev-erbα, cry1, per1) mRNA expressions in group B and D were significantly different from those in group A (all P<0. 05) . Expression of cry1 in group D was significantly higher than that in group C. In group C, rev-erbαmRNA expression was significantly down-regulated in comparison with group A (P<0. 05). Conclusion Constant light exposure exaggerates obesity, glycolipid metabolism abnormality, inflammation, and insulin resistance in high fat diet rats.

Objective:To explore associations of subclinical hypothyroidism (SCH) with endocrine metabolic characteristics in women with polycystic ovary syndrome (PCOS).Methods:A total of 321 women who were newly diagnosed as PCOS were recruited from two endocrine outpatient clinics.The diagnosis of PCOS was established according to the 2003 Rotterdam consensus criteria.Thyroid function was examined by chemiluminescent immunoassay.Patients who had normal free thyroxine (FT4) were divided into different SCH subgroups according to two thyroid stimulating hormone (TSH) cutoffpoints (4.2 and 2.5 mU/L).Endocrine metabolic characteristics in different subgroups were compared and analyzed.Results:In PCOS women with normal FT4,the patients with TSH ≥ 4.2 mU/L had higher prolactin (PRL),luteinizing hormone-to-follicle stimulating hormone ratio,and visceral adipose index (all P<0.05).There were trends toward an increase in triglyceride (P=0.085) and a decrease in high-density lipoprotein cholesterol (HDL-C) (P=0.060) in the patients with TSH ≥ 4.2 mU/L compared with that in the patients with TSH<4.2 mU/L.Also in PCOS women with normal FT4,the patients with TSH ≥ 2.5 mU/L had higher body mass index,PRL,triglyceride,visceral adipose index and lower HDL-C in comparison of that in the patients with TSH<2.5 mU/L (all P<0.05).Conclusion:SCH is associated with more severe endocrine abnormality,dyslipidemia,and visceral obesity in PCOS women.PCOS women with normal FT4 and endocrine metabolic characteristics are more prone to be different between the SCH group and the euthyroid group when setting 2.5 mU/L as a TSH cutoff for SCH,indicating that 2.5 mU/L is a good TSH cutoff for SCH in PCOS women.

OBJECTIVETo assess the association of single nucleotide polymorphisms (SNPs) of NLRP3 gene with metabolic syndrome (MetS).

METHODSA total of 885 subjects including 410 MetS patients and 475 healthy controls were recruited. MetS was defined based on the National Cholesterol Education Program in Adult Treatment Panel III criteria. Two common SNPs of the NLRP3 gene, rs10754558 and rs4612666, were detected using polymerase chain reaction-restriction fragment length polymorphism method.

RESULTSThe frequencies of G allele and GG genotype of the NLRP3 rs10754558 in the MetS group were significantly higher than those of the control group. Logistic regression analysis showed that the GG genotype (OR=2.223, 95%CI: 1.296-6.924, P=0.00034) and G allele (OR=1.440, 95%CI: 1.189-4.063, P=0.00028) were associated with increased risk of MetS. NLRP3 rs10754558 GG genotype was associated with higher level of insulin resistance and visceral adiposity index. No association of NLRP3 rs4612666 SNPs with susceptibility to MetS was identified in this population.

CONCLUSIONNLRP3 gene rs10754558 polymorphisms are associated with increased risk of MetS. The G allele and genotype GG are risk factors for MetS.

Adult ; Aged ; Carrier Proteins ; genetics ; Female ; Genotype ; Humans ; Insulin Resistance ; Logistic Models ; Male ; Metabolic Syndrome ; etiology ; genetics ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein ; Polymorphism, Single Nucleotide