The Role of a Glucagon-Like Peptide-1 Receptor Agonist in Visceral and Subcutaneous Fat Redistribution

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RA) are an ideal therapy for type 2 diabetes and recently, for obesity. In contrast to visceral fat, subcutaneous fat accumulation appears to be protective against metabolic syndrome. Here, we reported that liraglutide, a GLP-1RA redistributed visceral and subcutaneous fat via the tissue-specific modulation of lipid metabolism and stimulation of subcutaneous white adipose tissue (WAT) browning. We showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral WAT but elevated in subcutaneous WAT treated with liraglutide. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes displayed similar trends. Liraglutide down-regulated the expression levels of lipogenesis- and lipolysis-related genes but up-regulated the expression levels of β-oxidation-related genes in visceral WAT. In subcutaneous WAT, the expression levels of lipogenesis-related genes were up-regulated in both inguinal and cluneal WAT. However, the lipolysis-related gene expressed higher in inguinal WAT but lower in cluneal WAT, while the β-oxidation-related gene expressed lower in inguinal WAT but higher in cluneal WAT after liraglutide treatment. In addition, the uncoupling protein-1 was up-regulated in subcutaneous WAT. Thus, liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders. Disclosure L. Zhao: None. C. Zhu: None. M. Lu: None. C. Chen: None. Y. Chen: None. N. Wang: None. Y. Lu: None.