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

Gunduz M. K., KAYMAK G., Kanbur E., BERİKTEN D., ŞENER H.

TOXICOLOGY IN VITRO, vol.85, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 85
  • Publication Date: 2022
  • Doi Number: 10.1016/j.tiv.2022.105479
  • Journal Name: TOXICOLOGY IN VITRO
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Veterinary Science Database
  • Keywords: Obesity, Adipogenesis, 3T3-L1 cell line, Exenatide, CTRP3 gene, GLUCAGON-LIKE PEPTIDE-1, C1Q/TNF-RELATED PROTEIN-3 CTRP3, TYPE-2 DIABETES-MELLITUS, ADAPTIVE THERMOGENESIS, ARTERIAL STIFFNESS, GAMMA AGONIST, PPAR-GAMMA, TISSUE, GLP-1, ADIPOCYTES
  • Bursa Uludag University Affiliated: Yes

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-gamma 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-gamma gene expression indicate that exenatide is a promising new pharmaco-therapeutic agent in the treatment of obesity by regulating the expression of genes related to adipogenesis and lipogenesis and inducing apoptosis.