Glucagon-like peptide-1 (GLP-1) analogues aid weight loss that improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT that expresses the GLP-1 receptor (GLP-1R). The present study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT (SCAT) inflammatory and fibrotic responses, compared with weight loss by calorie reduction (control). Among the 39 participants with Type 2 diabetes recruited, 30 age-matched participants were randomized 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±1.72 kg, P=0.007) and significant reduction in visceral AT (VAT). It was more effective in lowering fasting glucose, in comparison with weight loss by dieting. However, tumour necrosis factor-α (TNFA) AT-expression (P=0.0005), macrophage chemoattractant protein-1 (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 cluster of differentiation 14 (CD14) expression (P=0.09) was found. Liraglutide treatment also increased expression of factors involved in extracellular matrix (ECM) deposition, transforming growth factor-β (TGFB) and collagen type 1 alpha 1 chain (COL1A1) (TGFB1: before 0.73±0.09 arbitrary units (AU), after 1.00±0.13 AU, P=0.006; COL1A1: 0.84±0.09 AU compared with 1.49±0.26 AU, 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.
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Phase contrast microscopy showing primary human mesangial cells in culture. Quantification of cell area showed that exposure of mesangial cells to the pro-fibrotic growth factor (TGF-β1) induced morphological cell expansion and hypertrophy, which was reversed following the overexpression of miR-378. Interestingly, transfection of a miR-378 inhibitor induced the expansion of mesangial cells, highlighting the regulatory role of miR-378 in mesangial hypertrophy. Please see the article by Wang et al. (pages 411-423).
Research Article|
February 15 2017
GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction
Emilie Pastel;
Emilie Pastel
1Diabetes and Obesity Research Group, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
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Laura J. McCulloch;
Laura J. McCulloch
1Diabetes and Obesity Research Group, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
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Rebecca Ward;
Rebecca Ward
1Diabetes and Obesity Research Group, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
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Shivam Joshi;
Shivam Joshi
1Diabetes and Obesity Research Group, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
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Kim M. Gooding;
Kim M. Gooding
2Diabetes and Vascular Medicine, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
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Angela C. Shore;
Angela C. Shore
2Diabetes and Vascular Medicine, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
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Katarina Kos
1Diabetes and Obesity Research Group, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
Correspondence: Katarina Kos (k.kos@exeter.ac.uk)
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Publisher: Portland Press Ltd
Received:
October 21 2016
Revision Received:
December 20 2016
Accepted:
December 22 2016
Accepted Manuscript online:
January 03 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (5): 343–353.
Article history
Received:
October 21 2016
Revision Received:
December 20 2016
Accepted:
December 22 2016
Accepted Manuscript online:
January 03 2017
Citation
Emilie Pastel, Laura J. McCulloch, Rebecca Ward, Shivam Joshi, Kim M. Gooding, Angela C. Shore, Katarina Kos; GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction. Clin Sci (Lond) 1 March 2017; 131 (5): 343–353. doi: https://doi.org/10.1042/CS20160803
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