Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet

Lipids. 2016 Dec;51(12):1375-1384. doi: 10.1007/s11745-016-4209-y. Epub 2016 Nov 1.

Abstract

Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low-carbohydrate high-fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low-carbohydrate high-fat diet (LCHFD) and low-carbohydrate high-fat diet plus metformin (LCHFD + MET) (100 mg kg-1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL-c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin-stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator-activated receptor (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), were assessed by RT-PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity-related diseases in metabolic syndrome.

Keywords: Adipose tissue; Lipogenesis; Metabolism; Metformin; Obesity.

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Administration, Oral
  • Animals
  • Biomarkers / blood*
  • Body Weight / drug effects
  • Diet, Carbohydrate-Restricted
  • Diet, High-Fat
  • Eating / drug effects
  • Fatty Acid Synthases / genetics
  • Gene Expression Regulation / drug effects
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Lipogenesis / drug effects*
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacology
  • Mice
  • Mice, Obese
  • Obesity / genetics
  • Obesity / metabolism*
  • PPAR gamma / genetics
  • Sterol Regulatory Element Binding Protein 1 / genetics

Substances

  • Biomarkers
  • Hypoglycemic Agents
  • PPAR gamma
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Metformin
  • Fatty Acid Synthases
  • Acetyl-CoA Carboxylase