Mitochondrial uncoupling proteins (UCPs) and obesity.
Obesity is now regarded as major public health problem worldwide. Research into this condition has been increasingly focussed on elucidating the cellular and molecular mechanisms regulating mammalian energy intake and expenditure. It is widely acknowledged that the brown adipose tissue (BAT) mitochondrial uncoupling protein (UCP1) plays a pivotal role in adaptive thermogenic responses. Two homologues of UCP1 (UCP2 and UCP3) have recently been identified and population-based genetic studies have linked them with basal metabolic rate, while in vitro studies report that both have proton transport activity and may thus be involved in regulation of energy homeostasis and hence obesity. However, evidence from genetically modified animal models indicates that UCP2 and UCP3 have no specific physiological thermogenic function in vivo, though they may still be useful therapeutic targets for obesity. Furthermore, their role in modulating levels of reactive oxygen species and glucose homeostasis is also being investigated.
Crowley
V
V
Departments of Medicine and Clinical Biochemistry, University of Cambridge, Level 4, Box 232, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, UK.
Vidal-Puig
A J
AJ
D002001:Adipose Tissue, Brown / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009765:Obesity / Q000503:physiopathology*; D011506:Proteins / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology; D014475:Uncoupling Agents / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3