miR‐34a−/− mice are susceptible to diet‐induced obesity

• Published in: Obesity (Silver Spring, Md.) Vol. 24; no. 8; pp. 1741 - 1751
• Main Authors: Lavery, Christopher A., Kurowska‐Stolarska, Mariola, Holmes, William M., Donnelly, Iona, Caslake, Muriel, Collier, Andrew, Baker, Andrew H., Miller, Ashley M.
• Format: Journal Article
• Language: English
• Published: United States John Wiley and Sons Inc 01.08.2016
• Subjects: Adipose Tissue - metabolism; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - metabolism; Animals; Diet, High-Fat; Interleukin-10 - metabolism; Liver - metabolism; Macrophages - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - metabolism; Obesity - metabolism; Original; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.21561

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.