Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes

Haojun Yang, Martina Ralle, Michael J. Wolfgang, Neha Dhawan, Jason L. Burkhead, Susana Rodriguez, Jack H. Kaplan, G. William Wong, Norman Haughey, Svetlana Lutsenko

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Copper (Cu) has emerged as an important modifier of body lipid metabolism. However, how Cu contributes to the physiology of fat cells remains largely unknown. We found that adipocytes require Cu to establish a balance between main metabolic fuels. Differentiating adipocytes increase their Cu uptake along with the ATP7A-dependent transport of Cu into the secretory pathway to activate a highly up-regulated amino-oxidase copper-containing 3 (AOC3)/semicarbazide-sensitive amine oxidase (SSAO); in vivo, the activity of SSAO depends on the organism’s Cu status. Activated SSAO oppositely regulates uptake of glucose and long-chain fatty acids and remodels the cellular proteome to coordinate changes in fuel availability and related downstream processes, such as glycolysis, de novo lipogenesis, and sphingomyelin/ceramide synthesis. The loss of SSAO-dependent regulation due to Cu deficiency, limited Cu transport to the secretory pathway, or SSAO inactivation shifts metabolism towards lipid-dependent pathways and results in adipocyte hypertrophy and fat accumulation. The results establish a role for Cu homeostasis in adipocyte metabolism and identify SSAO as a regulator of energy utilization processes in adipocytes.

Original languageEnglish (US)
Article numbere2006519
JournalPLoS Biology
Volume16
Issue number9
DOIs
StatePublished - Sep 2018

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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    Yang, H., Ralle, M., Wolfgang, M. J., Dhawan, N., Burkhead, J. L., Rodriguez, S., Kaplan, J. H., Wong, G. W., Haughey, N., & Lutsenko, S. (2018). Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes. PLoS Biology, 16(9), [e2006519]. https://doi.org/10.1371/journal.pbio.2006519