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


ABSTRACT: 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 ?, 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.

SUBMITTER: Shu L 

PROVIDER: S-EPMC5290165 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Shu Lingling L   Hoo Ruby L C RL   Wu Xiaoping X   Pan Yong Y   Lee Ida P C IP   Cheong Lai Yee LY   Bornstein Stefan R SR   Rong Xianglu X   Guo Jiao J   Xu Aimin A  

Nature communications 20170127


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 f  ...[more]

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