Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway.

BACKGROUND: Obesity is closely related to the metabolism of triacylglycerol (TG) in adipocytes. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are rate-limiting enzymes that control the hydrolysis of TG. Effects on ATGL and HSL to increase lipolysis may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicine plant Coptis chinensis. In the present study we show the effects of BBR on ATGL and HSL and explore the potential underlying mechanisms of these effects. METHODS: The TG content in cells was measured using a colorimetric assay. The expressions of HSL, ATGL and GPAT3 were evaluated by Western-blotting. The expression of ATGL was also evaluated by real-time PCR and radioimmunoassay. Compound C, an inhibitor of AMP-activated protein kinase (AMPK), was used to explore the possible pathway that involved in the effect of BBR on ATGL. RESULTS: TG content of differentiated 3T3-L1 cells was significantly decreased by more than 10% after treated with BBR. In differentiated 3T3-L1 adipocytes, BBR increased the expression of p-HSL and ATGL, and these effects were time-depended (p <0.01). The effect of BBR on ATGL expression could be abolished by Compound C which suggested that AMPK pathway was involved in the effects of BBR on p-HSL and ATGL. CONCLUSIONS: BBR could increase the expression of ATGL and therefore stimulate basal lipolysis in mature adipocytes through the associated mechanisms related to the AMPK pathway.

Therapeutic Effect of Metformin on Chemerin in Non-Obese Patients with Non-Alcoholic Fatty Liver Disease (NAFLD).

BACKGROUND: Chemerin is an important risk factor of insulin resistance. Non-alcoholic fatty liver has typical characteristics of insulin resistance. The aim of this study was to explore the potential role of chemerin in NAFLD. METHODS: 45 subjects included 22 control subjects (A group) and 23 subjects diagnosed with non-alcoholic fatty liver disease (B group) participated in the study. 23 patients in the NAFLD group received oral daily metformin at a dose of 20 mg/kg/day for 24 weeks follow-up. Chemerin and insulin resistance markers were determined at baseline and 24 weeks. RESULTS: The levels of WHR, BMI, FINS, HOMA-IR, TG, ALT, AST, and Chemerin in B group were significantly higher than A group. After 24 weeks of metformin treatment, the levels of WHR, AST, ALT, TG, chemerin and HOMA-IR were significantly reduced (p < 0.05) and other indexes were not changed significantly. Correlation analysis indicated that serum chemerin concentrations were positively correlated with BMI, WHR, HOMA-IR, FINS, TG, ALT, and AST levels. Logistic regression analysis showed chemerin, TG, and ALT were independent variables associated with NAFLD. CONCLUSIONS: These findings showed a significant increase of chemerin level in NAFLD patients. Metformin treatment can improve NAFLD and decrease the level of chemerin. Chemerin, TG, and ALT were independent variables associated with NAFLD.

Vaspin as a Risk Factor of Insulin Resistance in Obstructive Sleep Apnea-Hypopnea Syndrome in an Animal Model.

BACKGROUND: In this study, we aimed to establish a chronic intermittent hypoxia model in rats and explore the possible role of vaspin in insulin sensitivity. METHODS: Healthy male Wistar rats were randomly divided into two groups: normal control group (NC) and chronic intermittent hypoxia group (CIH). The NC group was raised under physiological conditions and the CIH group was kept in the plexiglass chamber between 9 am and 5 pm undergoing intermittent hypoxic challenge for 8 hours/day for 8 weeks. Arterial blood pressure of rats (tail cannulation) was measured before and after the study. Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), fasting insulin (FINS), vaspin, and leptin levels were measured. Vaspin mRNA expression in visceral adipose tissues was measured with Real Time-PCR. The protein levels of vaspin, Akt and phospho-Akt in visceral tissues were determined by Western-blot. RESULTS: At baseline, all the measurements in the CIH and NC groups were comparable. By the end of the experiment, the blood pressure of the CIH group was significantly higher than the NC group. The levels of FPG, FINS, TG, TC, leptin, and vaspin in the CIH group were significantly higher than in NC group. Plasma vaspin levels were correlated with FINS, HOMA-IR, and TG levels. Vaspin expression in both mRNA and protein levels in visceral adipose tissues of the CIH group were clearly higher than the NC group. Phospho-Akt protein level was decreased in visceral adipose tissues of the CIH group compared to the NC group. CONCLUSIONS: In the chronic intermittent hypoxia rat model, the expression of vaspin in visceral adipose tissues and plasma were increased, which were correlated with insulin resistance.

Changes of lipin1ß expression in gestational diabetes mellitus.

BACKGROUND: Lipin1ß is an adipokine proposed to be associated with insulin resistance (IR). Pregnancy is a physiologic state of progressive IR. The objective of the present study was to investigate the role of lipin1ß in the development of GDM. METHODS: A total of 40 pregnant women (22 normal and 18 with GDM) who delivered healthy infants at full-term (> 37 weeks gestation) were included. The mRNA and protein levels of lipin1ß in adipose tissues were determined by real-time RT-PCR and Western-blot. Plasma glucose, lipids, insulin, and estradiol (E2) levels were measured routinely at fasting state, and HOMA-IR was calculated accordingly. RESULTS: The lipin1ß expression in both mRNA and protein levels in SAT and VAT was lower in GDM patients than controls. Lipin1ß mRNA in VAT was negatively correlated with BMI (r = -0.505, p < 0.05), FINS (r = -0.539, p < 0.05), HOMA-IR (r = -0.574, p < 0.01), TG (r = -0.471, p < 0.05), and E2 (r = -0.564, p < 0.01). Lipin1ß mRNA expression in SAT was similar with VAT. Lipin1ß mRNA was not correlated with body weight gain or blood pressure. These results indicated that the lipin1ß expression in adipose tissues is down-regulated in patients with GDM. CONCLUSIONS: Lipin1ß might play a role in the pathogenesis of insulin resistance in GDM.

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease.

The present study was designed to identify the changes in microvesicle-dipeptidyl peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether there were correlations with the severity of diabetic kidney disease (DKD). A total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according to the urinary albumin/ creatinine ratio (UACR): microalbuminuria group (n = 50); macroalbuminuria group (n = 34) and normoalbuminuria group (n = 43), and 34 age- and sex-matched non-diabetic healthy subjects were selected as controls. Microvesicle-bound DPP IV and free urinary DPP IV were separated by a filtra-centrifugation method. The total microvesicles were captured by a specific monoclonal antibody, AD-1. DPP IV activity was determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly-Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels were determined by ELISA and Western blot. Our results showed that the microvesicle-bound type was the major form of DPP IV in urine; the urinary microvesicle-DPP IV excretion of each T2DM group was significantly higher compared with controls. The urinary microvesicle-DPP IV level was positively correlated with UACR in patients with T2DM. These findings suggest that the urinary level of microvesicle-bound DPP IV is associated with the severity of DKD.