Exenatide increases CTRP3 gene expression in adipose cells by inhibiting adipogenesis and induces apoptosis

Toxicol In Vitro. 2022 Dec:85:105479. doi: 10.1016/j.tiv.2022.105479. Epub 2022 Sep 21.

Abstract

Considering the rapidly increasing prevalence of obesity worldwide, the number of weight control drugs is very few. Incretin-based therapies are currently being developed to achieve weight control, and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) are used in incretin-based therapies. This study aimed to investigate the cytotoxicity of exenatide, a GLP-1A, on 3T3-L1 adipocytes and the effect of exenatide on the expression of adipogenesis-related genes, insulin and glucose levels, and apoptosis. Cytotoxic activity of exenatide on 3T3-L1 adipocytes was determined by MTT method. Gene expression levels were determined by qPCR. Apoptosis studies were performed on the Muse Cell Analyzer. C1q/TNF-related protein-3 (CTRP3) expression levels were found to be higher in exenatide treated adipocyte cells than in control cells (p < 0.001). Adipocyte cells treated with exenatide were found to have lower PPAR-γ gene expression levels when compared to control adipocyte cells (p < 0.001). Intracellular insulin (p < 0.001) and glucose levels were higher in 3T3-L1 adipocytes treated with exenatide compared to control adipocyte cells. Total apoptosis increased approximately 1.5 times as a result of exenatide administration. The increase in CTRP3 gene expression, which is thought to be a new biomarker for obesity, and the decrease in PPAR-γ gene expression indicate that exenatide is a promising new pharmacotherapeutic agent in the treatment of obesity by regulating the expression of genes related to adipogenesis and lipogenesis and inducing apoptosis.

Keywords: 3T3-L1 cell line; Adipogenesis; CTRP3 gene; Exenatide; Obesity.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes
  • Adipogenesis*
  • Alprostadil / metabolism
  • Alprostadil / pharmacology
  • Alprostadil / therapeutic use
  • Animals
  • Apoptosis
  • Cell Differentiation
  • Complement C1q / genetics
  • Complement C1q / metabolism
  • Complement C1q / pharmacology
  • Exenatide / genetics
  • Exenatide / pharmacology
  • Exenatide / therapeutic use
  • Gene Expression
  • Glucagon-Like Peptide-1 Receptor / genetics
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptide-1 Receptor / therapeutic use
  • Glucose / metabolism
  • Incretins* / metabolism
  • Incretins* / pharmacology
  • Incretins* / therapeutic use
  • Insulin / metabolism
  • Insulin / pharmacology
  • Mice
  • Obesity / drug therapy
  • Obesity / genetics
  • Obesity / metabolism
  • PPAR gamma / metabolism

Substances

  • Exenatide
  • Incretins
  • Alprostadil
  • Complement C1q
  • Glucagon-Like Peptide-1 Receptor
  • PPAR gamma
  • Insulin
  • Glucose