miR-34a(-/-) mice are susceptible to diet-induced obesity.
Obesity (Silver Spring)
; 24(8): 1741-51, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27377585
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/ebpß, 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.CONCLUSIONS:
These findings suggest a multifactorial role of miR-34a in controlling susceptibility to obesity, by regulating inflammatory and metabolic pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Dieta Hiperlipídica
/
Obesidade
Limite:
Animals
Idioma:
En
Revista:
Obesity (Silver Spring)
Assunto da revista:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Reino Unido