GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction

Glucagon-like peptide-1 (GLP-1) analogues aid weight loss which improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT which expresses GLP-1 receptors. This study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT inflammatory and fibrotic responses, compared to weight loss by calorie reduction (control). Among the 39 participants with type 2 diabetes recruited, 30 age-matched participants were randomised to 4 months treatment with Liraglutide (n=22) or calorie restriction-based on dietetic counselling (n=8). Assessments included clinical characteristics and repeated subcutaneous abdominal AT biopsies. Liraglutide resulted in weight loss in most participants (-3.12±1.72kg, p=0.007) and significant reduction in visceral AT. It was more effective in lowering fasting glucose, in comparison to weight loss by dieting. However TNFA AT-expression (p=0.0005), MCP-1 expression (p=0.027) and its serum levels (p=0.048) increased with Liraglutide, suggestive of an inflammatory response unlike in the diet arm in which a trend of lower CD14 expression (p=0.09) was found. Liraglutide treatment also increased expression of factors involved in ECM deposition, TGFbeta and Collagen-1 ( TGFB1 : before 0.73±0.09AU, after 1.00±0.13AU, p=0.006; COL1A1 : 0.84±0.09AU versus 1.49±0.26AU, p=0.026). Liraglutide thus appears to induce an inflammatory response in AT and influences ECM remodelling. Despite its superior effect on glycaemia, Liraglutide does not improve obesity-associated AT dysfunction in subcutaneous tissue. It is yet unclear whether this limits AT storage capacity for lipids. This may be of importance in patients being re-exposed to positive energy balance such as post GLP-1 discontinuation