Relationship between plasma free fatty acids and uncoupling protein-3 gene expression in skeletal muscle of obese subjects: in vitro evidence of a causal link

2002 ◽  
Vol 57 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Paolo Sbraccia ◽  
Monica D’Adamo ◽  
Frida Leonetti ◽  
Angela Buongiorno ◽  
Gianfranco Silecchia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Uncoupling Protein ◽  
Causal Link ◽  
Plasma Free Fatty Acids ◽  
Uncoupling Protein 3 ◽  
Obese Subjects

Uncoupling protein-3 expression in skeletal muscle and free fatty acids in obesity

The Lancet ◽  
1998 ◽  
Vol 351 (9120) ◽  
pp. 1933 ◽  
Author(s):  
Olivier Boss ◽  
Elisabetta Bobbioni-Harsch ◽  
Francoise Assimacopoulos-Jeannet ◽  
Patrick Muzzin ◽  
Robert Munger ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Uncoupling Protein ◽  
Uncoupling Protein 3

scholarly journals Developmental and Tissue-Specific Involvement of Peroxisome Proliferator-Activated Receptor-α in the Control of Mouse Uncoupling Protein-3 Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4695-4704 ◽  
Author(s):  
Neus Pedraza ◽  
Meritxell Rosell ◽  
Joan Villarroya ◽  
Roser Iglesias ◽  
Frank J. Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ucp3 Gene ◽  
Uncoupling Protein 3

Uncoupling protein-3 (UCP3) is a member of the mitochondrial carrier family expressed preferentially in skeletal muscle and heart. It appears to be involved in metabolic handling of fatty acids in a way that minimizes excessive production of reactive oxygen species. Fatty acids are powerful regulators of UCP3 gene transcription. We have found that the role of peroxisome proliferator-activated receptor-α (PPARα) on the control of UCP3 gene expression depends on the tissue and developmental stage. In adults, UCP3 mRNA expression is unaltered in skeletal muscle from PPARα-null mice both in basal conditions and under the stimulus of starvation. In contrast, UCP3 mRNA is down-regulated in adult heart both in fed and fasted PPARα-null mice. This occurs despite the increased levels of free fatty acids caused by fasting in PPARα-null mice. In neonates, PPARα-null mice show impaired UCP3 mRNA expression in skeletal muscle in response to milk intake, and this is not a result of reduced free fatty acid levels. The murine UCP3 promoter is activated by fatty acids through either PPARα or PPARδ but not by PPARγ or retinoid X receptor alone. PPARδ-dependent activation could be a potential compensatory mechanism to ensure appropriate expression of UCP3 gene in adult skeletal muscle in the absence of PPARα. However, among transcripts from other PPARα and PPARδ target genes, only those acutely induced by milk intake in wild-type neonates were altered in muscle or heart from PPARα-null neonates. Thus, PPARα-dependent regulation is required for appropriate gene regulation of UCP3 as part of the subset of fatty-acid-responsive genes in neonatal muscle and heart.

scholarly journals Up-Regulation of Uncoupling Protein 3 Gene Expression by Fatty Acids and Agonists for PPARs in L6 Myotubes

Endocrinology ◽  
2001 ◽  
Vol 142 (10) ◽  
pp. 4189-4194 ◽  
Author(s):  
Cheol Son ◽  
Kiminori Hosoda ◽  
Junichi Matsuda ◽  
Junji Fujikura ◽  
Shin Yonemitsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Uncoupling Protein ◽  
L6 Myotubes ◽  
Uncoupling Protein 3

scholarly journals Free Fatty Acids Impair FGF21 Action in HepG2 Cells

2015 ◽  
Vol 37 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Mohamed Asrih ◽  
Christophe Montessuit ◽  
Jacques Philippe ◽  
François R. Jornayvaz
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Free Fatty Acids ◽  
Hepg2 Cells ◽  
Lipid Lowering ◽  
Fibroblast Growth Factor 21 ◽  
Beneficial Effects ◽  
Positive Effects

Background/Aims: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). Methods: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. Results: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. Conclusion: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.

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