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Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation.

Authors: Zeng, X  Jedrychowski, MP  Chen, Y  Serag, S  Lavery, GG  Gygi, SP  Spiegelman, BM 
Citation: Zeng X, etal., Genes Dev. 2016 Aug 15;30(16):1822-36. doi: 10.1101/gad.285312.116. Epub 2016 Aug 26.
Pubmed: (View Article at PubMed) PMID:27566776
DOI: Full-text: DOI:10.1101/gad.285312.116

Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or beta-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways. On the one hand, LSD1 associates with PRDM16 to repress expression of white fat-selective genes. On the other hand, LSD1 represses HSD11B1 (hydroxysteroid 11-beta-dehydrogenase isozyme 1), a key glucocorticoid-activating enzyme, independently from PRDM16. Adipose-specific ablation of LSD1 impaired mitochondrial fatty acid oxidation capacity of the brown adipose tissue, reduced whole-body energy expenditure, and increased fat deposition, which can be significantly alleviated by simultaneously deleting HSD11B1. These findings establish a novel regulatory pathway connecting histone modification and hormone activation with mitochondrial oxidative capacity and whole-body energy homeostasis.

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RGD Object Information
RGD ID: 11568525
Created: 2016-12-07
Species: All species
Last Modified: 2016-12-07
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.