A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes.
A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes.
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DOI：
10.1038/ncomms14147
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发表时间：
2017-01-27
影响因子：
16.6
通讯作者：
Xu A
中科院分区：
文献类型：
--
作者：
Shu L;Hoo RL;Wu X;Pan Y;Lee IP;Cheong LY;Bornstein SR;Rong X;Guo J;Xu A
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 α, 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. The protein A-FABP is secreted from adipocytes and known to regulate glucose and lipid metabolism. Here the authors show A-FABP enhances thermogenesis by promoting the conversion of thyroxine T4 to the bioactive form, T3, in brown adipocytes, and by enhancing fatty acid uptake of brown fat.
