Brown adipocyte ATF4 activation improves thermoregulation and systemic metabolism.

Autor:	Paulo E; Cardiovascular Research Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA., Zhang Y; Cardiovascular Research Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA., Masand R; Cardiovascular Research Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA., Huynh TL; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143, USA., Seo Y; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143, USA., Swaney DL; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA., Soucheray M; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA., Stevenson E; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA., Jimenez-Morales D; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA., Krogan NJ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA., Wang B; Cardiovascular Research Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: biao.wang@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Sep 21; Vol. 36 (12), pp. 109742.
DOI:	10.1016/j.celrep.2021.109742
Abstrakt:	Cold-induced thermogenesis in endotherms demands adaptive thermogenesis fueled by mitochondrial respiration and Ucp1-mediated uncoupling in multilocular brown adipocytes (BAs). However, dietary regulation of thermogenesis in BAs isn't fully understood. Here, we describe that the deficiency of Leucine-rich pentatricopeptide repeat containing-protein (Lrpprc) in BAs reduces mtDNA-encoded ETC gene expression, causes ETC proteome imbalance, and abolishes the mitochondria-fueled thermogenesis. BA-specific Lrpprc knockout mice are cold resistant in a 4°C cold-tolerance test in the presence of food, which is accompanied by the activation of transcription factor 4 (ATF4) and proteome turnover in BAs. ATF4 activation genetically by BA-specific ATF4 overexpression or physiologically by a low-protein diet feeding can improve cold tolerance in wild-type and Ucp1 knockout mice. Furthermore, ATF4 activation in BAs improves systemic metabolism in obesogenic environment regardless of Ucp1's action. Therefore, our study reveals a diet-dependent but Ucp1-independent thermogenic mechanism in BAs that is relevant to systemic thermoregulation and energy homeostasis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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