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)
|
Text
118938.pdf - Published Version Available under License Creative Commons Attribution. 6MB |
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 Miller, Dr Ashley and Holmes, Dr William and Caslake, Professor Muriel and Kurowska-Stolarska, Professor 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
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 |
University Staff: Request a correction | Enlighten Editors: Update this record