High mitochondrial redox potential may promote induction and activation of UCP2 in hepatocytes during hepatothermic therapy.
Although uncoupling protein-1 is a key mediator of thermogenesis in activated brown fat, the more recently characterized uncoupling proteins-2 and -3 do not appear to influence basal metabolism, but rather may function to diminish excessive mitochondrial superoxide production when mitochondrial redox potential is high. Under these circumstances, superoxide within the mitochondrial matrix directly activates uncoupling protein-2 (UCP2), and may also promote induction of this protein. Normal healthy hepatocytes do not express UCP2, but this protein is induced in hepatocytes that are steatotic or that are treated with agents that boost superoxide production. It is proposed that induction and activation of UCP2 may play a role in the thermogenesis evoked by hepatothermic therapy, a strategy designed to decrease body fat by maximizing hepatic fatty acid oxidation. Under these conditions, high mitochondrial redox potential would be expected, and induction of UCP2's uncoupling activity would represent a homeostatically appropriate antioxidant response.
McCarty
Mark F
MF
NutriGuard Research, 1051 Hermes Avenue, Encinitas, CA 92024, USA. mccarty@pantox.com
D000818:Animals; D002331:Carnitine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002952:Citric Acid Cycle / Q000187:drug effects; D004359:Drug Therapy, Combination; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007473:Ion Channels; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D011522:Protons; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects*; D000071246:Uncoupling Protein 2; D015431:Weight Loss
D002951:Citrates; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011522:Protons; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D013481:Superoxides; D019289:Pyruvic Acid; C007999:hydroxycitric acid; D002331:Carnitine