[Expression of Sirtuin 1 in visceral adipose tissue in Tibetan mini-pigs with obesity and insulin resistance induced by high fat/cholesterol diet].

ABSTRACT

OBJECTIVE: To investigate the role of Sirt1 in visceral adipose tissue in Tibetan mini-pigs with obesity and insulin resistance induced by high fat/cholesterol diet. METHODS: Twelve male Tibetan mini-pigs were divided into 2 groups randomly normal control (NC) group, high-fat/cholesterol (HFC) diet group, 6 in each group. After 16 weeks of modeling, fasting body weight and body mass index (BMI) were measured. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured in anterior venous blood, and atherosclerosis index (AI) was calculated. Meanwhile, intravenous glucose tolerance test was conducted to observe the changes of blood glucose and insulin, and the area under the curve (AUC) was calculated. After euthanasia, visceral fat rate was detected, and visceral fat tissue was taken for histopathological observation and fat cell diameter analysis. RT-PCR was used to observe the mRNA expression levels of Sirtuin1 (Sirt1), insulin-like growth factor-1 (IGF-1), glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor γ (PPARγ), peroxisome proliferator-activated receptor γ-assisted activator 1α (PGC-1α), forkhead box protein O1 (FoxO1), lipolysis-related gene hormone-sensitive lipase (HSL), and fat synthesis-related gene fatty acid synthase (FASN)changes in adipose tissue. RESULTS: Compared with the NC group, the body weight, BMI, TC, LDL-C, HDL-C, AI and visceral fat rate were significantly increased after 16 weeks of high-fat/cholesterol induction in Tibetan mini-pigs(P＜0.05,P＜0.01). Meanwhile, the glucose tolerance curve was significantly delayed and the area under the curve of blood glucose and insulin was significantly increased (P＜0.05). HE pathological observation and quantitative analysis showed that fat cells were hypertrophy and the average cell diameter was increased significantly (P＜0.01). In addition, the mRNA expression levels of Sirt1,PGC-1α, GLUT4, and HSL were all decreased in varying degrees in adipose tissue, among which the mRNA expressions of Sirt1 and HSL were significantly decreased (P＜0.05), while the mRNA expressions of FOXO1, IGF-1, PPARγ, and FASN were significantly increased (P＜0.05, P＜0.01). CONCLUSION: Tibetan mini-pigs were induced by high fat/cholesterol diet to form obesity model with phenotypic characteristics such as lipid disorder and insulin resistance, whereas Sirt1 plays a key role in visceral fat deposition and insulin sensitivity reduction in obese Tibetan mini-pigs.