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.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Yang H,Ralle M,Wolfgang MJ,Dhawan N,Burkhead JL,Rodriguez S,Kaplan JH,Wong GW,Haughey N,Lutsenko Sdoi
10.1371/journal.pbio.2006519subject
Has Abstractpub_date
2018-09-10 00:00:00pages
e2006519issue
9eissn
1544-9173issn
1545-7885pii
pbio.2006519journal_volume
16pub_type
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