Adipose tissue and insulin-resistance. Beneficial effects of glp-1 agonists

Abstract

Insulin-resistance (IR) is characterized by adipose tissue (AT) expansion associated withextracellular matrix (ECM) remodeling. Metalloproteinases (MMPs) are endopeptidasesinvolved in adipogenesis and angiogenesis, and they are proposed as pharmacologicaltargets. Liraglutide (L), a glucagon-like peptide type 1 agonist, has emerged for themanagement of IR, and its effects on AT are still investigated. Aim: to evaluate the effect ofL on MMPs activity in an animal model of IR. Methods: male Wistar rats (180-200 g) weredivided in: Control (C, n=11) fed with standard diet, and sucrose rich diet group (SRD,n=14) fed with standard diet and sucrose 30% in drinking water during 15 weeks. Then,both groups were subdivided according to subcutaneous administration of L (0.6mg/kg/day) for 5 weeks. The study was approved by the Ethic Committee-FFYB (UBA).Serum glucose, and lipid and lipoprotein profile were measured. Visceral AT (perirrenal,intestinal and epididymal) was removed and weighed. In epididymal AT (EAT) histologicalcharacteristics, MMPs activity by gelatinolytic zymography and antioxidants enzymes(SOD and Catalase) were evaluated. Results: as expected, SRD presented higher visceralAT mass (p<0.05), TG and glucose levels (p<0.05) than C. In SRD+L group, a significantdecrease in body weight (p<0.01), EAT mass (p<0.01), TG (p=0.045) and glucose (p=0.05)levels compared to SRD was observed. As expected, SRD presented lower density oflarger adipocytes than C (p<0.05). In turn, vascular density was lower in SRD (p<0.05 vsC). L decreased adipocyte size (p<0.05 vs SRD), as well as significantly increasedvascular density in SRD+L (p<0.001 vs SRD). MMP-2 activity decreased in EAT from SRD(p<0.05 vs C) and increased in SDR+L (p<0.05 vs SRD). L decreased SOD activity in EATin the SRD group (p<0.01) with no change in catalase activity. Conclusions: In IR,liraglutide would improve AT functionality by preventing disfavored features during MECremodeling.