GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction
Abstract
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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GLP-1 RA showed distinct anti-inflammatory signatures and effects on adipose tissue, even in studies where weight reduction was restricted or where exenatide was compared to weight-matched dietary intervention.
“Fourth, GLP-1 RA showed distinct anti-inflammatory signatures and effects on adipose tissue, even in studies where weight reduction was restricted or where exenatide was compared to weight-matched dietary intervention (33).”
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- Authors
- Pastel, E., McCulloch, L. J., Ward, R., Joshi, S., Gooding, K. M., Shore, A. C., & Kos, K.
- Affiliations
- University of Exeter (GB)
- Corresponding author
- Kos, Katarina
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2017-02-15
- Volume
- 131
- Issue
- 5
- Pages
- 343-353
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W2567189085
- Cited by
- 49
- References
- 50
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 2
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Funders
- European Foundation for the Study of Diabetes
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- GLP-1 receptor agonists, liraglutide, obesity, adipose tissue dysfunction, subcutaneous adipose tissue, adipose tissue inflammation, adipose tissue fibrosis, extracellular matrix remodeling, caloric restriction, type 2 diabetes, visceral adipose tissue, TNF-α, MCP-1, CD14, TGF-beta
- MeSH terms
- Liraglutide, Adipose Tissue, Aged, Diabetes Mellitus, Type 2, Extracellular Matrix, Humans, Hypoglycemic Agents, Inflammation, Male, Middle Aged, Obesity, Leptin, Glucagon-Like Peptide 1, Adiponectin
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