title: 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 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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Ruby L C
authors.initials: RL
authors.lastname: Hoo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Ida P C
authors.initials: IP
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Lai Yee
authors.initials: LY
authors.lastname: Cheong
authors.affiliation: Department of Medicine, University of Dresden, 01307 Dresden, Germany.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Joint Laboratory of Guangdong and Hong Kong on Metabolic Diseases, Guangdong Pharmaceutical University, 510000 Guangzhou, China.
authors.forename: Xianglu
authors.initials: X
authors.lastname: Rong
authors.affiliation: Joint Laboratory of Guangdong and Hong Kong on Metabolic Diseases, Guangdong Pharmaceutical University, 510000 Guangzhou, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D000071518:Liver X Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000502:physiology; D022722:Thermogenesis / Q000502:physiology*; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D050556:Fatty Acid-Binding Proteins; D007453:Iodide Peroxidase; D000071518:Liver X Receptors; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C493411:Fabp4 protein, mouse; C000605214:Nr1h3 protein, mouse