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Kaltenecker, D. ; Spirk, K.* ; Ruge, F.* ; Grebien, F.* ; Herling, M.* ; Rupprecht, A.* ; Kenner, L.* ; Pohl, E.E.* ; Mueller, K.M.* ; Moriggl, R.*

STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue.

Mol. Metab. 40:101026 (2020)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Jak-stat ; Beta-adrenergic Signalling ; Thermogenesis ; Temperature Maintenance; Cold-induced Thermogenesis; Fat Development; Lipolysis; Beige; Adipocytes; Metabolism; Adipogenesis; Deficiency; Activation; Proteins

ISSN (print) / ISBN 2212-8778

e-ISSN 2212-8778

Journal Molecular Metabolism

Quellenangaben Volume: 40, Article Number: 101026

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Cancer (IDC)

Grants European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme
DLR
EU Transcan-2 consortium ERANET-PLL via the FWF
Austrian Science Fund (FWF)