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

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Authors
Pastel, E.
McCulloch, L. J.
Ward, R.
Joshi, S.
Gooding, K. M.
Shore, Angela
Kos, K.
Journal
Clinical Science
Type
Journal Article
Publisher
Portland Press
Rights
Archived with thanks to Clinical Science
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.
Citation
GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction 2017:CS20160803 Clinical Science
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