Premium
Diet‐induced obesity causes insulin resistance in mouse brown adipose tissue
Author(s) -
RobertsToler Carla,
O'Neill Brian T.,
Cypess Aaron M.
Publication year - 2015
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21134
Subject(s) - insulin resistance , adipose tissue , obesity , medicine , endocrinology , brown adipose tissue
Objective Diet‐induced obesity (DIO) causes several pathophysiological changes in adipose tissue. Increased inflammation reduces white adipose tissue (WAT) insulin sensitivity and contributes to the development of diabetes. However, little is known about how DIO alters the function of brown adipose tissue (BAT), an organ that consumes calories by β3‐adrenergic receptor (AR)‐mediated thermogenesis and helps regulate energy balance. Methods To test the effects of DIO on BAT, we fed 6‐week‐old C57BL/6 mice either a normal chow diet (NCD) or a high‐fat diet (HFD). After 16 additional weeks, we measured body fat, WAT, and BAT mRNA expression, glucose tolerance, and rates of glucose uptake in response to insulin and the β3‐AR agonist mirabegron. Results Compared with NCD, HFD increased body fat and impaired glucose tolerance. Both WAT and BAT had higher mRNA levels of markers of inflammation, including TNFα and F4/80. Insulin signaling in BAT and WAT was reduced, with decreased Akt phosphorylation. Diet‐normalized BAT glucose uptake rates were lower in response to mirabegron. Conclusions These results support a model in which DIO leads to BAT inflammation and insulin resistance, leading to a broader impairment of BAT function.