Chinese medicine Jiangzhuo mixture regulates glucose and lipid metabolism in obese rats through TLR4/I κB α/NF- κB signaling pathway / 浙江大学学报·医学版

OBJECTIVES@#To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats.@*METHODS@#Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues.@*RESULTS@#Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05).@*CONCLUSIONS@#Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.

Effect of EPO on PRDM16, FGF21 expression and STAT phosphorylation of brown adipose tissue in HFD mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of erythropoietin (EPO) on blood glucoseand plasma insulin level, index of insulin resistance (HOMA-IR), introperitoneal glucose tolerance test (IPGTT), the mRNA and protein level of PR domain-containing 16 (PRDM16), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), fibroblast growth factor 21 (FGF21) of brown adipose tissue (BAT) in mice fed with high fat diet (HFD) in order to provide clues for the mechanism of obesity and complication.@*METHODS@#Twenty C57BL/6J male mice fed with HFD were randomly divided into control group (HFD-Con) and EPO group (HFD-EPO), mice in the two groups were injected intraperitoneally normal saline and EPO (200 IU/kg) res pectively, 3 times per week for consecutive 4 weeks.Then the body weight, blood glucose, plasma insulin level, HOMA-IR and IPGTT were detected.The mRNA and protein level of PRDM16, FGF21, p-STAT3/STAT3 in brown adipose tissue were detected by real-time quantitative RT-PCR and Western blot respectively.@*RESULTS@#After intraperitoneal injection of EPO for 4 weeks, the body weight of the mice in HFD-EPO and HFD-Con groups was (26.65±0.85) g and (31.50±1.6 0) g respectively.The blood glucose of the mice in HFD-EPO group[(62.79±8.09) mg/dl]was significantly decreased compared with that in HFD-Con group[(91.06±9.86) mg/dl].The plasmainsulin level in HFD-EPO group[(10.56±1.06)μU/ml]was significantly decreased compared with that in HFD-Con group[(13.2±1.1)μU/ml, < 0.01].The level of IPGTT in HFD-EPO group was significantly ameliorated and th e HOMA-IR decreased compared with those in HFD-Con group.The mRNA and protein expressions of PRDM16, FGF21 and the level of STAT3 of brown adipose tissue in HFD-E PO group were increased obviously.And there was no difference of FGF21 mRNA content in liver and FGF21 content in plasmabetween the two groups.@*CONCLUSIONS@#EPO could promote differentiation of brown adipose tissue by increase in the express ion of PRDM16, and decrease the blood glucose level, ameliorate glucose metabolism in obses mice.

The investigation on the inhibitive effect of berberine on gene expression of FSP27 to improve visceral white adipose tissue insulin resistance in type 2 diabetic hamsters / 天津医药

Objective To study the effects of berberine (BBR) on the gene mRNA expression of fat-specific protein 27 (FSP27) and PR domain containing 16 (PRDM16) signal pathway in visceral white adipose tissues (VWAT) from type 2 dia? betic (T2DM) Chinese hamsters, and explore the related mechanisms. Methods The obese insulin-resistant (OIR) hamster model was induced by high-fat diet, and T2DM hamster model was created by OIR hamster model injected with low-dose streptozotocin. The control group was fed with standard laboratory chow. After the induction, the hamsters were randomly di?vided into control, OIR, obese T2DM and BBR-treated T2DM groups. After nine-week BBR treatment, real-time quantita?tive PCR was used to measure the gene mRNA expression changes of VWAT FSP27 and PRDM16 signal pathway and their target genes from different groups. Results Compared with control group, the gene mRNA expressions of PRDM16, CtBP-1, CtBP-2, C/EBPβ, PPARγ, PGC1α, PGC-1β and brown adipose tissue-specific genes such as UCP-1, Cidea, Elovl3, PPARα, and Acox, Cpt1 and Acadm were decreased and that of FSP27 and white adipose tissue-specific genes including Resistin, MEST and Serpina3k were increased in VWAT in OIR and obese T2DM groups. BBR treatment down-regulated FSP27 expression, enhanced PRDM16 signal pathway, and induced the gene mRNA expression of brown adipose tissue-spe?cific genes in VWAT of obese T2DM group to develop browning gene phenotype of VWAT, and then improved fat-induced insulin resistance. Conclusion The decreased FSP27 expression and increased PRDM16 expression are involved in the molecular mechanisms of browning of visceral white adipose tissues induced by BBR, and which contributes to improve ab?normal lipids metabolism and fat-induced insulin resistance in VWAT by enhancing consumption of energy as heat to re?store VWAT function.