Mitochondrial uncoupling as a target in the treatment of obesity.
OBJECTIVE
Obesity is associated with many health problems and its prevalence is rapidly increasing worldwide. Very few pharmaceutical compounds are available for obesity treatment. Strategies for the development of compounds can be targeted to the outcomes of reduced dietary energy intake and/or increased energy expenditure/thermogenesis. In this review, we focus on recent discoveries that advance our understanding of mitochondrial uncoupling as a target for the treatment of obesity. There are various mechanisms whereby uncoupling can occur and for the purpose of this review, we elaborate upon the uncoupling that can occur (1) through the original uncoupling protein, UCP1, in brown adipocytes, or in 'converted' white adipose tissue, and (2) in skeletal muscle.


RESULTS
Studies have identified a number of novel receptors and regulatory proteins involved in the emergence of brown adipocytes in white adipose tissue. Molecular and pharmacologic approaches in knockout and transgenic mice have demonstrated their relevance to obesity treatment. Recent research into uncoupling mechanisms in skeletal muscle indicates that uncoupling can occur through basal and inducible processes.


CONCLUSIONS
Uncoupling is a naturally occurring phenomenon whose underlying mechanisms require substantial further study for the development of antiobesity therapies.
Costford
Sheila
S
Department of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
Gowing
Adrienne
A
Harper
Mary-Ellen
ME
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1