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

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, [2003]-
    • Subject Terms:
      Adipocytes/*enzymology ; Adipocytes/*metabolism ; Amine Oxidase (Copper-Containing)/*metabolism ; Copper/*metabolism; 3T3-L1 Cells ; Animals ; Base Sequence ; Biological Transport ; Cell Differentiation ; Cell Shape ; Cell Size ; Copper/deficiency ; Copper-Transporting ATPases/metabolism ; Energy Metabolism ; Enzyme Activation ; Fatty Acids/biosynthesis ; Glucose/metabolism ; Homeostasis ; Hypertrophy ; Male ; Mice ; Proteomics ; Rats, Wistar ; Secretory Pathway ; Triglycerides/metabolism
    • 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.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Grant Information:
      R01 DK071865 United States DK NIDDK NIH HHS; R01 DK084171 United States DK NIDDK NIH HHS; R01 NS072241 United States NS NINDS NIH HHS; R56 DK071865 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Atp7a protein, mouse)
      0 (Fatty Acids)
      0 (Triglycerides)
      789U1901C5 (Copper)
      EC 1.4.3.21 (Amine Oxidase (Copper-Containing))
      EC 7.2.2.8 (Copper-Transporting ATPases)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20180911 Date Completed: 20190422 Latest Revision: 20241112
    • Publication Date:
      20241112
    • Accession Number:
      PMC6130853
    • Accession Number:
      10.1371/journal.pbio.2006519
    • Accession Number:
      30199530