Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition - A link with insulin resistance

Citation
S. Samec et al., Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition - A link with insulin resistance, DIABETES, 48(2), 1999, pp. 436-441
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETES
ISSN journal
0012-1797 → ACNP
Volume
48
Issue
2
Year of publication
1999
Pages
436 - 441
Database
ISI
SICI code
0012-1797(199902)48:2<436:PGEOSM>2.0.ZU;2-K
Abstract
UCP2 and UCP3 are two recently cloned genes with high sequence homology to the gene for uncoupling protein (UCP)-1, which regulates thermogenesis in b rown adipose tissue. In the context of the current debate about whether UCP 2 and UCP3 in the skeletal muscle may also function as mediators of thermog enesis or as regulators of lipids as fuel substrate, we have examined their mRNA expressions in rat gastrocnemius muscle in response to dietary manipu lations known to differentially affect thermogenesis during the phase of we ight recovery after starvation, Compared with ad libitum-fed control rats, the refeeding of isocaloric amounts of a low-fat (high-carbohydrate) diet r esulted in lower energy expenditure and lower mRNA levels of muscle UCP2 an d UCP3. This downregulation of UCP homologs was abolished by the refeeding of a high-fat diet, even though energy expenditure was significantly lower during refeeding on the high-fat; than on the low-fat diet. Furthermore, ma jor alterations in the fatty acid composition of the refeeding diet in favo r of n-6 polyunsaturated or medium-chain fatty acids resulted hn significan t increases in energy expenditure, but with no significant changes in the e xpression of skeletal muscle UCP homologs. Regression analysis of gastrocne mius UCP mRNA levels against parameters that included body composition, ene rgy expenditure, and plasma levels-of free fatty acids (FFAs), Insulin, and glucose as well as the increase in plasma glucose after a glucose load, re vealed that only the latter (an index of insulin resistance) could explain the variability in muscle UCP2, and UCP3 mRNA expressions (r = 0.41, P < 0. 02; r = 0.45, P < 0.01, respectively). Taken together, these data are at va riance with a role for skeletal muscle UCP2 and UCP3 In dietary regulation (or modulation) of thermogenesis. However, they are consistent with the not ion that these UCP homologs may function as regulators of lipids as fuel su bstrate and raise the possibility that high-fat induced upregulation of mus cle UCP2 and UCP3 may be more closely linked to insulin resistance than to changes in circulating.