Selenoprotein P-mediated reductive stress impairs cold-induced thermogenesis in brown fat.

Autor:	Oo SM; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Oo HK; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Takayama H; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan; Life Sciences Division, Engineering and Technology Department, Kanazawa University, Kanazawa, Ishikawa, Japan., Ishii KA; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan; Department of System Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan., Takeshita Y; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Goto H; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Nakano Y; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Kohno S; Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan., Takahashi C; Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan., Nakamura H; Department of Environmental and Preventive Medicine, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan., Saito Y; Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan., Matsushita M; Department of Nutrition, Tenshi College, Sapporo, Japan., Okamatsu-Ogura Y; Laboratory of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan., Saito M; Laboratory of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan., Takamura T; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. Electronic address: ttakamura@med.kanazawa-u.ac.jp.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Mar 29; Vol. 38 (13), pp. 110566.
DOI:	10.1016/j.celrep.2022.110566
Abstrakt:	Reactive oxygen species (ROS) activate uncoupler protein 1 (UCP1) in brown adipose tissue (BAT) under physiological cold exposure and noradrenaline (NA) stimulation to increase thermogenesis. However, the endogenous regulator of ROS in activated BAT and its role in pathological conditions remain unclear. We show that serum levels of selenoprotein P (SeP; encoded by SELENOP) negatively correlate with BAT activity in humans. Physiological cold exposure downregulates Selenop in BAT. Selenop knockout mice show higher rectal temperatures and UCP1 sulfenylation during cold exposure. SeP treatment to brown adipocytes eliminated the NA-induced mitochondrial ROS by upregulating glutathione peroxidase 4 and impaired cellular thermogenesis. A high-fat/high-sucrose diet elevates serum SeP levels and diminishes the elevated NA-induced thermogenesis in BAT-Selenop KO mice. Therefore, SeP is the intrinsic factor inducing reductive stress that impairs thermogenesis in BAT and may be a potential therapeutic target for obesity and diabetes. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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