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Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes

Thermogenic adipocytes generate heat to maintain body temperature against hypothermia in response to cold. Although tight regulation of thermogenesis is required to prevent energy sources depletion, the molecular details that tune thermogenesis are not thoroughly understood. Here, we demonstrate tha...

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Autores principales: Han, Ji Seul, Jeon, Yong Geun, Oh, Minsik, Lee, Gung, Nahmgoong, Hahn, Han, Sang Mun, Choi, Jeehye, Kim, Ye Young, Shin, Kyung Cheul, Kim, Jiwon, Jo, Kyuri, Choe, Sung Sik, Park, Eun Jung, Kim, Sun, Kim, Jae Bum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174489/
https://www.ncbi.nlm.nih.gov/pubmed/35672324
http://dx.doi.org/10.1038/s41467-022-30925-0
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author Han, Ji Seul
Jeon, Yong Geun
Oh, Minsik
Lee, Gung
Nahmgoong, Hahn
Han, Sang Mun
Choi, Jeehye
Kim, Ye Young
Shin, Kyung Cheul
Kim, Jiwon
Jo, Kyuri
Choe, Sung Sik
Park, Eun Jung
Kim, Sun
Kim, Jae Bum
author_facet Han, Ji Seul
Jeon, Yong Geun
Oh, Minsik
Lee, Gung
Nahmgoong, Hahn
Han, Sang Mun
Choi, Jeehye
Kim, Ye Young
Shin, Kyung Cheul
Kim, Jiwon
Jo, Kyuri
Choe, Sung Sik
Park, Eun Jung
Kim, Sun
Kim, Jae Bum
author_sort Han, Ji Seul
collection PubMed
description Thermogenic adipocytes generate heat to maintain body temperature against hypothermia in response to cold. Although tight regulation of thermogenesis is required to prevent energy sources depletion, the molecular details that tune thermogenesis are not thoroughly understood. Here, we demonstrate that adipocyte hypoxia-inducible factor α (HIFα) plays a key role in calibrating thermogenic function upon cold and re-warming. In beige adipocytes, HIFα attenuates protein kinase A (PKA) activity, leading to suppression of thermogenic activity. Mechanistically, HIF2α suppresses PKA activity by inducing miR-3085-3p expression to downregulate PKA catalytic subunit α (PKA Cα). Ablation of adipocyte HIF2α stimulates retention of beige adipocytes, accompanied by increased PKA Cα during re-warming after cold stimuli. Moreover, administration of miR-3085-3p promotes beige-to-white transition via downregulation of PKA Cα and mitochondrial abundance in adipocyte HIF2α deficient mice. Collectively, these findings suggest that HIF2α-dependent PKA regulation plays an important role as a thermostat through dynamic remodeling of beige adipocytes.
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spelling pubmed-91744892022-06-09 Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes Han, Ji Seul Jeon, Yong Geun Oh, Minsik Lee, Gung Nahmgoong, Hahn Han, Sang Mun Choi, Jeehye Kim, Ye Young Shin, Kyung Cheul Kim, Jiwon Jo, Kyuri Choe, Sung Sik Park, Eun Jung Kim, Sun Kim, Jae Bum Nat Commun Article Thermogenic adipocytes generate heat to maintain body temperature against hypothermia in response to cold. Although tight regulation of thermogenesis is required to prevent energy sources depletion, the molecular details that tune thermogenesis are not thoroughly understood. Here, we demonstrate that adipocyte hypoxia-inducible factor α (HIFα) plays a key role in calibrating thermogenic function upon cold and re-warming. In beige adipocytes, HIFα attenuates protein kinase A (PKA) activity, leading to suppression of thermogenic activity. Mechanistically, HIF2α suppresses PKA activity by inducing miR-3085-3p expression to downregulate PKA catalytic subunit α (PKA Cα). Ablation of adipocyte HIF2α stimulates retention of beige adipocytes, accompanied by increased PKA Cα during re-warming after cold stimuli. Moreover, administration of miR-3085-3p promotes beige-to-white transition via downregulation of PKA Cα and mitochondrial abundance in adipocyte HIF2α deficient mice. Collectively, these findings suggest that HIF2α-dependent PKA regulation plays an important role as a thermostat through dynamic remodeling of beige adipocytes. Nature Publishing Group UK 2022-06-07 /pmc/articles/PMC9174489/ /pubmed/35672324 http://dx.doi.org/10.1038/s41467-022-30925-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Han, Ji Seul
Jeon, Yong Geun
Oh, Minsik
Lee, Gung
Nahmgoong, Hahn
Han, Sang Mun
Choi, Jeehye
Kim, Ye Young
Shin, Kyung Cheul
Kim, Jiwon
Jo, Kyuri
Choe, Sung Sik
Park, Eun Jung
Kim, Sun
Kim, Jae Bum
Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
title Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
title_full Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
title_fullStr Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
title_full_unstemmed Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
title_short Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
title_sort adipocyte hif2α functions as a thermostat via pka cα regulation in beige adipocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174489/
https://www.ncbi.nlm.nih.gov/pubmed/35672324
http://dx.doi.org/10.1038/s41467-022-30925-0
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