한빛사 논문
Ji Seul Han1, Yong Geun Jeon1, Minsik Oh2, Gung Lee1, Hahn Nahmgoong1, Sang Mun Han1, Jeehye Choi1, Ye Young Kim1, Kyung Cheul Shin1, Jiwon Kim1, Kyuri Jo3, Sung Sik Choe1, Eun Jung Park4, Sun Kim5,6,7 & Jae Bum Kim1,*
1Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea. 2School of Software Convergence, Myongji University, Seoul, South Korea. 3Department of Computer Engineering, Chungbuk National University, Cheongju, South Korea. 4Cancer Immunology Branch, Department of System Cancer Science, National Cancer Center, Goyang, South Korea. 5Department of Computer Science and Engineering, Seoul National University, Seoul, South Korea. 6Institute of Engineering Research, Seoul National University, Seoul, South Korea. 7AIGENDRUG Co., Ltd., Seoul, South Korea.
*Corresponding author.
Abstract
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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