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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620196
Title:
GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction
Authors:
Pastel, E.; McCulloch, L. J.; Ward, R.; Joshi, S.; Gooding, K. M.; Shore, Angela ( 0000-0003-3039-308x ) ; Kos, K.
Abstract:
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
Publisher:
Portland Press
Journal:
Clinical Science
Issue Date:
3-Jan-2017
URI:
http://hdl.handle.net/11287/620196
DOI:
10.1042/CS20160803
Additional Links:
http://clinsci.org/lookup/doi/10.1042/CS20160803
Type:
Journal Article
Language:
en
ISSN:
0143-5221; 1470-8736
Appears in Collections:
Cardiology; Honorary contracts publications; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPastel, E.en
dc.contributor.authorMcCulloch, L. J.en
dc.contributor.authorWard, R.en
dc.contributor.authorJoshi, S.en
dc.contributor.authorGooding, K. M.en
dc.contributor.authorShore, Angelaen
dc.contributor.authorKos, K.en
dc.date.accessioned2017-01-19T12:09:25Z-
dc.date.available2017-01-19T12:09:25Z-
dc.date.issued2017-01-03-
dc.identifier.citationGLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction 2017:CS20160803 Clinical Scienceen
dc.identifier.issn0143-5221-
dc.identifier.issn1470-8736-
dc.identifier.doi10.1042/CS20160803-
dc.identifier.urihttp://hdl.handle.net/11287/620196-
dc.description.abstractGlucagon-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.en
dc.language.isoenen
dc.publisherPortland Pressen
dc.relation.urlhttp://clinsci.org/lookup/doi/10.1042/CS20160803en
dc.rightsArchived with thanks to Clinical Scienceen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleGLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunctionen
dc.typeJournal Articleen
dc.identifier.journalClinical Scienceen
dc.type.versionIn press (epub ahead of print)en
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