Liraglutide induced browning of visceral white adipose through regulation of miRNAs in high-fat-diet-induced obese mice.

Abstract

Obesity is characterized by excessive accumulation of white adipose tissue (WAT). Conversely, brown adipose tissue is protective against obesity. We recently reported liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), could inhibit high-fat-diet-induced obesity by browning of WAT. However, the molecular mechanism involved is not well defined. Hence, we aimed to explore whether GLP-1RA could promote brown remodeling in WAT by regulating miRNAs. After the obesity model was successfully constructed, C57BL/6J mice were treated with liraglutide (200 μg/kg/d) or equivoluminal saline subcutaneously for 12 weeks. Then, the deposition of abdominal fat was measured by CT scanning. At the end of the treatments, glucose and insulin tolerance in mice were assessed. Serum lipid levels were monitored and epididymal WAT (eWAT) were collected for analysis. Quantitative real-time PCR and western blot analyses were conducted to evaluate the expression of genes and miRNAs associated with white fat browning. Liraglutide significantly reduced body weight and visceral fat mass. Levels of lipid profile were also improved. Liraglutide upregulated the expression of browning-related genes in eWAT. Meanwhile, the expression level of miRNAs (miR-196a and miR-378a) positively associated with the browning of WAT were increased, while the expression of miR-155, miR-199a, and miR-382 negatively related with browning of WAT were decreased. Our findings suggest that liraglutide could promote brown remodeling of visceral WAT by bi-regulating miRNAs; this might be one of the mechanisms underlying its effect on weight loss.