Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis

Brown and beige adipocytes are specialized to dissipate energy as heat. Sgk2, encoding a serine/threonine kinase, has been identified as a brown and beige adipocyte-specific gene in rodents and humans; however, its function in brown/beige adipocytes remains unraveled. Here, we examined the regulatio...

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Autores principales:	Chul-Hong Park, Jiyoung Moon, Minsung Park, Helia Cheng, Jisu Lee, Ji Suk Chang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	brown adipocytes beige adipocytes beta-adrenergic receptor thermogenesis SGK2 kinase PPARGC1A Physiology QP1-981
Acceso en línea:	https://doaj.org/article/28532b24e7b148e1b07cb4dd92d85871
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id	oai:doaj.org-article:28532b24e7b148e1b07cb4dd92d85871
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spelling	oai:doaj.org-article:28532b24e7b148e1b07cb4dd92d858712021-12-01T02:44:12ZProtein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis1664-042X10.3389/fphys.2021.780312https://doaj.org/article/28532b24e7b148e1b07cb4dd92d858712021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.780312/fullhttps://doaj.org/toc/1664-042XBrown and beige adipocytes are specialized to dissipate energy as heat. Sgk2, encoding a serine/threonine kinase, has been identified as a brown and beige adipocyte-specific gene in rodents and humans; however, its function in brown/beige adipocytes remains unraveled. Here, we examined the regulation and role of Sgk2 in brown/beige adipose tissue thermogenesis. We found that transcriptional coactivators PGC-1α and NT-PGC-1α activated by the β3 adrenergic receptor-cAMP-PKA pathway are recruited to the Sgk2 promoter, triggering Sgk2 transcription in response to cold. SGK2 elevation was closely associated with increased serine/threonine phosphorylation of proteins carrying the consensus RxRxxS/T phosphorylation site. However, despite cold-dependent activation of SGK2, mice lacking Sgk2 exhibited normal cold tolerance at 4°C. In addition, Sgk2+/+ and Sgk2−/− mice induced comparable increases in energy expenditure during pharmacological activation of brown and beige adipose tissue with a β3AR agonist. In vitro loss- and gain-of-function studies further demonstrated that Sgk2 ablation or activation does not alter thermogenic gene expression and mitochondrial respiration in brown adipocytes. Collectively, our results reveal a new signaling component SGK2, although dispensable for cold-induced thermogenesis that adds an additional layer of complexity to the β3AR signaling network in brown/beige adipose tissue.Chul-Hong ParkJiyoung MoonMinsung ParkHelia ChengJisu LeeJi Suk ChangFrontiers Media S.A.articlebrown adipocytesbeige adipocytesbeta-adrenergic receptorthermogenesisSGK2 kinasePPARGC1APhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	brown adipocytes beige adipocytes beta-adrenergic receptor thermogenesis SGK2 kinase PPARGC1A Physiology QP1-981
spellingShingle	brown adipocytes beige adipocytes beta-adrenergic receptor thermogenesis SGK2 kinase PPARGC1A Physiology QP1-981 Chul-Hong Park Jiyoung Moon Minsung Park Helia Cheng Jisu Lee Ji Suk Chang Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis
description	Brown and beige adipocytes are specialized to dissipate energy as heat. Sgk2, encoding a serine/threonine kinase, has been identified as a brown and beige adipocyte-specific gene in rodents and humans; however, its function in brown/beige adipocytes remains unraveled. Here, we examined the regulation and role of Sgk2 in brown/beige adipose tissue thermogenesis. We found that transcriptional coactivators PGC-1α and NT-PGC-1α activated by the β3 adrenergic receptor-cAMP-PKA pathway are recruited to the Sgk2 promoter, triggering Sgk2 transcription in response to cold. SGK2 elevation was closely associated with increased serine/threonine phosphorylation of proteins carrying the consensus RxRxxS/T phosphorylation site. However, despite cold-dependent activation of SGK2, mice lacking Sgk2 exhibited normal cold tolerance at 4°C. In addition, Sgk2+/+ and Sgk2−/− mice induced comparable increases in energy expenditure during pharmacological activation of brown and beige adipose tissue with a β3AR agonist. In vitro loss- and gain-of-function studies further demonstrated that Sgk2 ablation or activation does not alter thermogenic gene expression and mitochondrial respiration in brown adipocytes. Collectively, our results reveal a new signaling component SGK2, although dispensable for cold-induced thermogenesis that adds an additional layer of complexity to the β3AR signaling network in brown/beige adipose tissue.
format	article
author	Chul-Hong Park Jiyoung Moon Minsung Park Helia Cheng Jisu Lee Ji Suk Chang
author_facet	Chul-Hong Park Jiyoung Moon Minsung Park Helia Cheng Jisu Lee Ji Suk Chang
author_sort	Chul-Hong Park
title	Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis
title_short	Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis
title_full	Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis
title_fullStr	Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis
title_full_unstemmed	Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis
title_sort	protein kinase sgk2 is induced by the β3 adrenergic receptor-camp-pka-pgc-1α/nt-pgc-1α axis but dispensable for brown/beige adipose tissue thermogenesis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/28532b24e7b148e1b07cb4dd92d85871
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Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis

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