Uncoupling protein 3 and fatty acid metabolism

Citation
Ag. Dulloo et al., Uncoupling protein 3 and fatty acid metabolism, BIOCH SOC T, 29, 2001, pp. 785-791
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL SOCIETY TRANSACTIONS
ISSN journal
0300-5127 → ACNP
Volume
29
Year of publication
2001
Part
6
Pages
785 - 791
Database
ISI
SICI code
0300-5127(2001)29:<785:UP3AFA>2.0.ZU;2-Z
Abstract
A role for uncoupling protein (UCP) 3 in fatty acid metabolism is reviewed within the context of our proposal, first put forward in 1998, that this ho mologue of UCP1 may be involved in the regulation of lipids as fuel substra te rather than in the mediation of thermogenesis. Since then, the demonstra tions of muscle-type differences in UCP3 gene regulation in response to die tary manipulations (starvation, high-fat feeding) or to pharmacological int erferences with the flux of lipid substrates between adipose-tissue stores and skeletal-muscle mitochondrial oxidation are all in accord with this pro posed role for UCP3 in regulating lipids as fuel substrate. However, given the current limitations of gene-knockout technology for evaluating/interpre ting the functional importance of genes encoding mitochondrial membrane pro teins, the transition from 'associative' to 'cause-and-effect' evidence for a physiological role of UCP3 in regulating fatty acid metabolism will have to await the development of assays that are sensitive to changes in UCP3 a ctivity. Furthermore, in evaluating the physiological regulators of UCP3, t he available evidence points to the existence of adipose-derived factor(s) which, independently of circulating levels of free fatty acids, initiates e vents leading to the transcription of genes encoding UCP3 and key enzymes o f lipid oxidation in the fast glycolytic or fast oxidative-glycolytic muscl es, i.e. in the bulk of the skeletal-muscle mass. It is proposed that in ti ssues where UCP3 co-exists with UCP2 (skeletal muscle, brown adipose tissue , heart) they may act in concert in the overall regulation of lipid oxidati on, concomitant to the prevention of lipid-induced oxidative damage.