miR-34a-/- mice are susceptible to diet-induced obesity

Lavery, C. A., Kurowska-Stolarska, M. , Holmes, W. , Donnelly, I., Caslake, M., Collier, A., Baker, A. H. and Miller, A. M. (2016) miR-34a-/- mice are susceptible to diet-induced obesity. Obesity, 24(8), pp. 1741-1751. (doi:10.1002/oby.21561) (PMID:27377585) (PMCID:PMC4979678)

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Abstract

Objective: MicroRNA (miR)−34a regulates inflammatory pathways, and increased transcripts have been observed in serum and subcutaneous adipose of subjects who have obesity and type 2 diabetes. Therefore, the role of miR-34a in adipose tissue inflammation and lipid metabolism in murine diet-induced obesity was investigated. Methods: Wild-type (WT) and miR-34a−/− mice were fed chow or high-fat diet (HFD) for 24 weeks. WT and miR-34a−/− bone marrow-derived macrophages were cultured in vitro with macrophage colony-stimulating factor (M-CSF). Brown and white preadipocytes were cultured from the stromal vascular fraction (SVF) of intrascapular brown and epididymal white adipose tissue (eWAT), with rosiglitazone. Results: HFD-fed miR-34a−/− mice were significantly heavier with a greater increase in eWAT weight than WT. miR-34a−/− eWAT had a smaller adipocyte area, which significantly increased with HFD. miR-34a−/− eWAT showed basal increases in Cd36, Hmgcr, Lxrα, Pgc1α, and Fasn. miR-34a−/− intrascapular brown adipose tissue had basal reductions in c/ebpα and c/ebpβ, with in vitro miR-34a−/− white adipocytes showing increased lipid content. An F4/80high macrophage population was present in HFD miR-34a−/− eWAT, with increased IL-10 transcripts and serum IL-5 protein. Finally, miR-34a−/− bone marrow-derived macrophages showed an ablated CXCL1 response to tumor necrosis factor-α. Conclusions: These findings suggest a multifactorial role of miR-34a in controlling susceptibility to obesity, by regulating inflammatory and metabolic pathways.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:LAVERY, Christopher and Baker, Professor Andrew and Holmes, Dr William and Caslake, Professor Muriel and Miller, Dr Ashley and Kurowska-Stolarska, Dr Mariola and Donnelly, Mrs Iona
Authors: Lavery, C. A., Kurowska-Stolarska, M., Holmes, W., Donnelly, I., Caslake, M., Collier, A., Baker, A. H., and Miller, A. M.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Obesity
Publisher:Wiley
ISSN:1930-7381
ISSN (Online):1930-739X
Published Online:05 July 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Obesity 24(8):1741-1751
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
492453BHF 4 Year PhD ProgrammeAnna DominiczakBritish Heart Foundation (BHF)FS/11/79/29329RI CARDIOVASCULAR & MEDICAL SCIENCES
617101Investigation into the role of IL-33-responsive natural helper cells in adipose tissue inflammation during obesityAshley MillerMedical Research Council (MRC)MR/K019716/1RI CARDIOVASCULAR & MEDICAL SCIENCES
514111MicroRNA in monocytes: its contribution to the pathogenesis of arthritis and cardiovascular co-morbidityMariola Kurowska-StolarskaArthritis Research UK (ARC)19213III -IMMUNOLOGY