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Titolo:
Overexpression of UCP3 in cultured human muscle lowers mitochondrial membrane potential, raises ATP/ADP ratio, and favors fatty acid versus glucose oxidation
Autore:
Garcia-Martinez, C; Sibille, B; Solanes, G; Darimont, C; Mace, K; Villarroya, F; Gomez-Foix, AM;
Indirizzi:
Univ Barcelona, Fac Quim, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain Univ Barcelona Barcelona Spain E-08028 iol Mol, E-08028 Barcelona, Spain Nestle Res Ctr, CH-1000 Lausanne, Switzerland Nestle Res Ctr Lausanne Switzerland CH-1000 H-1000 Lausanne, Switzerland Univ Lyon 1, Lab Physiol & Regulat Energet Cellulaires & Mol, F-69622 Villeurbanne, France Univ Lyon 1 Villeurbanne France F-69622 ol, F-69622 Villeurbanne, France
Titolo Testata:
FASEB JOURNAL
fascicolo: 9, volume: 15, anno: 2001,
pagine: NIL_18 - NIL_35
SICI:
0892-6638(200107)15:9<NIL_18:OOUICH>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
UNCOUPLING PROTEIN-3 GENE; BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; EXPRESSION; HEPATOCYTES; OBESITY; 2,4-DINITROPHENOL; THERMOGENESIS; ACTIVATION; TRANSPORT;
Keywords:
oleate; glycolytic rate; nutrient oxidation; glycolysis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Gomez-Foix, AM Univ Barcelona, Fac Quim, Dept Bioquim & Biol Mol, Marti & Franques 1, E-08028 Barcelona, Spain Univ Barcelona Marti & Franques 1 Barcelona Spain E-08028
Citazione:
C. Garcia-Martinez et al., "Overexpression of UCP3 in cultured human muscle lowers mitochondrial membrane potential, raises ATP/ADP ratio, and favors fatty acid versus glucose oxidation", FASEB J, 15(9), 2001, pp. NIL_18-NIL_35

Abstract

The skeletal muscle mitochondrial uncoupling protein-3 (UCP3) promotes substrate oxidation, but direct evidence for its metabolic role is lacking. Here, we show that UCP3 overexpression in cultured human muscle cells decreased mitochondrial membrane potential (Delta Psim). Despite this, the ATP content was not significantly decreased compared with control cells, whereas ADP content was reduced and thus the ATP/ADP ratio raised. This finding was in contrast with the effect caused by the chemical protonophoric uncoupler,CCCP, which lowered Delta Psim, ATP, and the ATP/ADP ratio. UCP3-overexpression enhanced oxidation of oleate, regardless of the presence of glucose, whereas etomoxir, which blocks fatty acid entry to mitochondria, suppressedthe UCP3 effect. Glucose oxidation was stimulated in UCP3-overexpressing cells, but this effect was inhibited by oleate. UCP3 caused weak increase ofboth 2-Deoxyglucose uptake and glycolytic rate, which differed from the marked stimulation by CCCP. We concluded that UCP3 promoted nutrient oxidation by lowering Delta Psim and enhanced fatty acid-dependent inhibition of glucose oxidation. Unlike the uncoupler CCCP, however, UCP3 raised the ATP/ADP ratio and modestly increased glucose uptake and glycolysis. We propose that this differential effect provides a biological significance to UCP3, which is up-regulated in metabolic stress situations where it could be involved in nutrient partitioning.

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Documento generato il 01/04/20 alle ore 01:49:28