A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes

作者：Shu, Lingling; Hoo, Ruby L. C.^*; Wu, Xiaoping; Pan, Yong; Lee, Ida P. C.; Cheong, Lai Yee; Bornstein, Stefan R.; Rong, Xianglu; Guo, Jiao; Xu, Aimin^*

来源：Nature Communications, 2017, 8(1): 14147.

DOI：10.1038/ncomms14147

• ACID-BINDING PROTEIN
• DIET-INDUCED OBESITY
• X RECEPTOR-ALPHA
• E-DEFICIENT MICE
• ADIPOSE-TISSUE
• NONSHIVERING THERMOGENESIS
• APOLIPOPROTEIN-E
• CARDIOVASCULAR-DISEASE
• INSULIN-RESISTANCE
• SENSITIVE LIPASE

The adipokine adipocyte fatty acid-binding protein (A-FABP) has been implicated in obesity-related cardio-metabolic complications. Here we show that A-FABP increases thermogenesis by promoting the conversion of T4 to T3 in brown adipocytes. We find that A-FABP levels are increased in both white (WAT) and brown (BAT) adipose tissues and the bloodstream in response to thermogenic stimuli. A-FABP knockout mice have reduced thermogenesis and whole-body energy expenditure after cold stress or after feeding a high-fat diet, which can be reversed by infusion of recombinant A-FABP. Mechanistically, A-FABP induces the expression of type-II iodothyronine deiodinase in BAT via inhibition of the nuclear receptor liver X receptor alpha, thereby leading to the conversion of thyroid hormone from its inactive form T4 to active T3. The thermogenic responses to T4 are abrogated in A-FABP KO mice, but enhanced by A-FABP. Thus, A-FABP acts as a physiological stimulator of BAT-mediated adaptive thermogenesis.

• 出版日期2017-1-27
• 单位广东药科大学; 医药生物技术国家重点实验室