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Research Article | Spotlight

Hypoxia Restrains Lipid Utilization via Protein Kinase A and Adipose Triglyceride Lipase Downregulation through Hypoxia-Inducible Factor

Ji Seul Han, Jung Hyun Lee, Jinuk Kong, Yul Ji, Jiwon Kim, Sung Sik Choe, Jae Bum Kim
Ji Seul Han
aNational Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea
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Jung Hyun Lee
aNational Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea
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Jinuk Kong
aNational Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea
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Yul Ji
aNational Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea
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Jiwon Kim
aNational Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea
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Sung Sik Choe
aNational Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea
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Jae Bum Kim
aNational Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea
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DOI: 10.1128/MCB.00390-18
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ABSTRACT

Oxygen is a key molecule for efficient energy production in living organisms. Although aerobic organisms have adaptive processes to survive in low-oxygen environments, it is poorly understood how lipolysis, the first step of energy production from stored lipid metabolites, would be modulated during hypoxia. Here, we demonstrate that fasting-induced lipolysis is downregulated by hypoxia through the hypoxia-inducible factor (HIF) signaling pathway. In Caenorhabditis elegans and mammalian adipocytes, hypoxia suppressed protein kinase A (PKA)-stimulated lipolysis, which is evolutionarily well conserved. During hypoxia, the levels of PKA activity and adipose triglyceride lipase (ATGL) protein were downregulated, resulting in attenuated fasting-induced lipolysis. In worms, HIF stabilization was sufficient to moderate the suppressive effect of hypoxia on lipolysis through ATGL and PKA inhibition. These data suggest that HIF activation under hypoxia plays key roles in the suppression of lipolysis, which might preserve energy resources in both C. elegans and mammalian adipocytes.

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Hypoxia Restrains Lipid Utilization via Protein Kinase A and Adipose Triglyceride Lipase Downregulation through Hypoxia-Inducible Factor
Ji Seul Han, Jung Hyun Lee, Jinuk Kong, Yul Ji, Jiwon Kim, Sung Sik Choe, Jae Bum Kim
Molecular and Cellular Biology Jan 2019, 39 (2) e00390-18; DOI: 10.1128/MCB.00390-18

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Hypoxia Restrains Lipid Utilization via Protein Kinase A and Adipose Triglyceride Lipase Downregulation through Hypoxia-Inducible Factor
Ji Seul Han, Jung Hyun Lee, Jinuk Kong, Yul Ji, Jiwon Kim, Sung Sik Choe, Jae Bum Kim
Molecular and Cellular Biology Jan 2019, 39 (2) e00390-18; DOI: 10.1128/MCB.00390-18
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KEYWORDS

ATGL
HIF
PKA
hypoxia
lipolysis

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