Universität zu Köln

Kaltenecker, Doris, Spirk, Katrin, Ruge, Frank, Grebien, Florian ORCID: 0000-0003-4289-2281, Herling, Marco, Rupprecht, Anne, Kenner, Lukas ORCID: 0000-0003-2184-1338, Pohl, Elena E., Mueller, Kristina M. and Moriggl, Richard (2020). STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue. Mol. Metab., 40. AMSTERDAM: ELSEVIER. ISSN 2212-8778

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Abstract

Objective: Increasing energy expenditure through activation of brown adipose tissue (BAT) thermogenesis is an attractive approach to counteract obesity. It is therefore essential to understand the molecular mechanisms that control BAT functions. Until now several members of the Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway have been implicated as being relevant for BAT physiology. However, whether the STAT family member STAT5 is important for the thermogenic property of adipose tissues is unknown. Therefore, we have investigated the role of STAT5 in thermogenic fat in this paper. Methods: We performed metabolic and molecular analyses using mice that harbor an adipocyte-specific deletion of Stat5a/b alleles. Results: We found that STAT5 is necessary for acute cold-induced temperature maintenance and the induction of lipid mobilization in BAT following beta(3)-adrenergic stimulation. Moreover, mitochondrial respiration of primary differentiated brown adipocytes lacking STAT5 was diminished. Increased sensitivity to cold stress upon STAT5 deficiency was associated with reduced expression of thermogenic markers including uncoupling protein 1 (UCP1), while decreased stimulated lipolysis was linked to decreased protein kinase A (PKA) activity. Additionally, brown remodeling of white adipose tissue was diminished following chronic beta(3)-adrenergic stimulation, which was accompanied by a decrease in mitochondrial performance. Conclusion: We conclude that STAT5 is essential for the functionality and the beta-adrenergic responsiveness of thermogenic adipose tissue. (C) 2020 The Author(s). Published by Elsevier GmbH.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaltenecker, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Spirk, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruge, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Grebien, Florian UNSPECIFIED orcid.org/0000-0003-4289-2281 UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Rupprecht, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Kenner, Lukas UNSPECIFIED orcid.org/0000-0003-2184-1338 UNSPECIFIED Pohl, Elena E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Kristina M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moriggl, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-317634
DOI:	10.1016/j.molmet.2020.101026
Journal or Publication Title:	Mol. Metab.
Volume:	40
Date:	2020
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2212-8778
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLD-INDUCED THERMOGENESIS; FAT DEVELOPMENT; LIPOLYSIS; BEIGE; ADIPOCYTES; METABOLISM; ADIPOGENESIS; DEFICIENCY; ACTIVATION; PROTEINS Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31763