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

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 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.

Metformin counteracts glucose-dependent lipogenesis and impairs transdeamination in the liver of gilthead sea bream (Sparus aurata)

“…However, the fact that S. aurata treated with metformin plus glucose presented lower SREBP1, Lpin1, and PGC1␤ mRNA levels than glucose-treated fish, points to downregulation of hepatic lipogenesis as a result of metformin action to reduce blood glucose levels in the hyperglycemic state. Metformin-dependent downregulation of SREBP1 expression and lipogenesis is consistent with previous observations in mammals (19,28,41,47), but contrasts with results reported for rainbow trout, which indicated that dietary metformin increases expression of lipogenic enzymes in the liver when rainbow trout were fed highcarbohydrate diets (31). Indeed, the administration of metformin together with insulin upregulated SREBP1 expression in the liver of rainbow trout fed high-carbohydrate diets, while metformin alone did not affect SREBP1 mRNA levels (33).…”

Dietary α-lactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in high-fat diet-fed mice

“…A similar reduction in fasn gene expression has been noted in a previous study ( 21 ) . On the contrary, other studies show that HFD intake increases fasn and acc in the adipose tissue ( 51 – 53 ) . The reasons for these discrepancies are unclear, but we speculate that contributing factors can include different genetic background, age, diet (composition and duration) and different housing environment.…”

Pterostilbene Inhibits Dyslipidemia-Induced Activation of Progenitor Adipose Gene Under High-Fat Diet and Radiation Stressor

“…Thus, increased levels of SREBP-1c boost adipogenic gene expression, fatty acid synthesis, and triglyceride production. 39 In adipose tissue of the HFD +IR rat group, treatment with either PS or Orlistat prevents adipogenesis and endorses lipolysis. Moreover, Orlistat moderately inhibits triglyceride hydrolysis, consequently diminishing the absorption of monoglycerides and free fatty acid.…”