title: miR-34a(-/-) mice are susceptible to diet-induced obesity.
abstract: 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.
  
  
  
  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.
  
  
  
  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 F4/80(high) 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.
  
  
  
  These findings suggest a multifactorial role of miR-34a in controlling susceptibility to obesity, by regulating inflammatory and metabolic pathways.
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lavery
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Mariola
authors.initials: M
authors.lastname: Kurowska-Stolarska
authors.affiliation: Glasgow Experimental MRI Centre, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
authors.forename: William M
authors.initials: WM
authors.lastname: Holmes
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Iona
authors.initials: I
authors.lastname: Donnelly
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Muriel
authors.initials: M
authors.lastname: Caslake
authors.affiliation: Ayr Hospital, National Health Service: Ayrshire & Arran, Ayr, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Collier
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Miller
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D016753:Interleukin-10 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10