Insulin therapy stimulates lipid synthesis and improves endocrine functions of adipocytes in dietary obese C57BL/6 mice

Abstract

Aim: To evaluate whether insulin intervention could affect the metabolic and endocrine functions of adipose tissue.

Methods: C57BL/6 mice were fed on a high-fat-diet for 12-16 weeks to induce insulin resistance. Insulin intervention was administered in the high-fat-diet mice for 4 weeks at 12 weeks (early insulin treatment) or 16 weeks (late insulin treatment). Intraperitoneal glucose tolerance tests were performed before and after insulin treatment. Expression levels of factors involved in the triglyceride synthesis and endocrine functions of adipose tissue including phosphoenolpyruvate carboxykinase (PEPCK-C), fatty acid synthase (FAS), aquaporin 7 (AQP7), adiponectin, visfatin, and interleukin-6 (IL-6) were determined by Western blot.

Results: In the obese mice, glucose tolerance was impaired; triglyceride content was increased in the liver tissue; protein expression of FAS and adiponectin was decreased; expression of visfatin was increased in adipose tissue. After 4-week insulin treatment, glucose tolerance was improved; triglyceride content was decreased in the liver and skeletal muscle; expression of PEPCK-C, FAS, and adiponectin was increased in the adipose tissue; IL-6 and AQP7 expression was reduced in the fat. Early insulin treatment had better effect in increasing the expression of FAS and PEPCK-C and decreasing the expression of IL-6.

Conclusion: These results indicate that insulin can target adipocytes for improvement of insulin sensitivity through stimulating triglyceride synthesis and partly improving endocrine functions.

Figure 1

Metabolic parameters among groups. (A) Body weight of C57BL/6 mice given a high-fat diet or a norma diet. ^bP<0.05, ^cP<0.01 vs NC group. (B) Intraperitoneal glucose tolerance tests (IPGTT) performed before intervention (IPGTT1). ^bP<0.05 vs NC group. (C) IPGTT performed after different intervention (IPGTT2). ^bP<0.05 vs NC group; ^eP<0.05 vs FC group. (D) Comparison in fasting TC level among groups. (E) Comparison in fasting TG level among groups. (F) Comparison in fasting FFA level among groups. (G) Comparison in TG content in the liver tissue among groups. (H) Comparison in TG content in the muscle tissue among groups.

Figure 2

FAS, PEPCK-C, AQP7 expression levels in adipose tissue of C57BL/6 mice. (Aa) Fatty acid synthase (FAS) expression levels in adipose tissue in C57BL/6 mice detected by Western blot. (Ab) Graphic representation of relative density of FAS protein levels in adipose tissue, which were normalized to those of β-actin. (Ba). Phosphoenolpyruvate carboxykinase (PEPCK-C) expression levels in adipose tissue in C57BL/6 mice detected by Western blot. (Bb) Graphic representation of relative density of PEPCK-C protein levels in adipose tissue, which were normalized to those of β-actin. (Ca) Aquaporin 7 (AQP7) expression levels in adipose tissue in C57BL/6 mice detected by Western blot. (Cb) Graphic representation of relative density of AQP7 protein levels in adipose tissue, which were normalized to those of β-actin.

Figure 3

Adiponectin, visfatin, and IL-6 expression levels in adipose tissue of C57BL/6 mice. (Aa) Adiponectin expression levels in adipose tissue in C57BL/6 mice detected by Western blot. (Ab) Graphic representation of relative density of adiponectin protein levels in adipose tissue, which were normalized to those of β-actin. (Ba) Visfatin expression levels in adipose tissue in C57BL/6 mice detected by Western blot. (Bb) Graphic representation of relative density of visfatin protein levels in adipose tissue, which were normalized to those of β-actin. (Ca) Interleukin-6 (IL-6) expression levels in adipose tissue in C57BL/6 mice detected by Western blot. (Cb) Graphic representation of relative density of IL-6 protein levels in adipose tissue, which were normalized to those of β-actin.