PPARs in the Control of Uncoupling Proteins Gene Expression

Villarroya, Francesc; Iglesias, Roser; Giralt, Marta

doi:https://doi.org/10.1155/2007/74364

PPAR Research

On this page

Abstract References Copyright Related Articles

Special Issue

PPARS and Obesity

View this Special Issue

Review Article | Open Access

Volume 2007 | Article ID 074364 | https://doi.org/10.1155/2007/74364

PPARs in the Control of Uncoupling Proteins Gene Expression

Francesc Villarroya,¹Roser Iglesias,¹and Marta Giralt¹

Academic Editor: Sander Kersten

Received31 Jul 2006

Revised18 Oct 2006

Accepted18 Oct 2006

Published26 Nov 2006

Abstract

Uncoupling proteins (UCPs) are mitochondrial membrane transporters involved in the control of energy conversion in mitochondria. Experimental and genetic evidence relate dysfunctions of UCPs with metabolic syndrome and obesity. The PPAR subtypes mediate to a large extent the transcriptional regulation of the UCP genes, with a distinct relevance depending on the UCP gene and the tissue in which it is expressed. UCP1 gene is under the dual control of PPARγ and PPARα in relation to brown adipocyte differentiation and lipid oxidation, respectively. UCP3 gene is regulated by PPARα and PPARδ in the muscle, heart, and adipose tissues. UCP2 gene is also under the control of PPARs even in tissues in which it is the predominantly expressed UCP (eg, the pancreas and liver). This review summarizes the current understanding of the role of PPARs in UCPs gene expression in normal conditions and also in the context of type-2 diabetes or obesity.

References

M. Del Mar Gonzalez-Barroso, D. Ricquier, and A.-M. Cassard-Doulcier, “The human uncoupling protein-1 gene (UCP1): present status and perspectives in obesity research,” Obesity Reviews, vol. 1, no. 2, pp. 61–72, 2000.
View at: Publisher Site | Google Scholar
S. Rousset, M.-C. Alves-Guerra, J. Mozo et al., “The biology of mitochondrial uncoupling proteins,” Diabetes, vol. 53, no. suppl 1, pp. S130–S135, 2004.
View at: Google Scholar
J. Nedergaard, D. Ricquier, and L. P. Kozak, “Uncoupling proteins: current status and therapeutic prospects,” EMBO Reports, vol. 6, no. 10, pp. 917–921, 2005.
View at: Publisher Site | Google Scholar
M. D. Brand and T. C. Esteves, “Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3,” Cell Metabolism, vol. 2, no. 2, pp. 85–93, 2005.
View at: Publisher Site | Google Scholar
J. C. Clapham, J. R. S. Arch, H. Chapman et al., “Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean,” Nature, vol. 406, no. 6794, pp. 415–418, 2000.
View at: Publisher Site | Google Scholar
S. Krauss, C.-Y. Zhang, and B. B. Lowell, “The mitochondrial uncoupling-protein homologues,” Nature Reviews Molecular Cell Biology, vol. 6, no. 3, pp. 248–261, 2005.
View at: Publisher Site | Google Scholar
A. Valmaseda, M. C. Carmona, M. J. Barberá et al., “Opposite regulation of PPAR- $a$ and - $?$ gene expression by both their ligands and retinoic acid in brown adipocytes,” Molecular and Cellular Endocrinology, vol. 154, no. 1-2, pp. 101–109, 1999.
View at: Publisher Site | Google Scholar
E. D. Rosen, C. J. Walkey, P. Puigserver, and B. M. Spiegelman, “Transcriptional regulation of adipogenesis,” Genes and Development, vol. 14, no. 11, pp. 1293–1307, 2000.
View at: Google Scholar
W. He, Y. Barak, A. Hevener et al., “Adipose-specific peroxisome proliferator-activated receptor $?$ knockout causes insulin resistance in fat and liver but not in muscle,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 15712–15717, 2003.
View at: Publisher Site | Google Scholar
T. Imai, R. Takakuwa, S. Marchand et al., “Peroxisome proliferator-activated receptor $?$ is required in mature white and brown adipocytes for their survival in the mouse,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 13, pp. 4543–4547, 2004.
View at: Publisher Site | Google Scholar
H. G. Linhart, K. Ishimura-Oka, F. DeMayo et al., “C/EBP $a$ is required for differentiation of white, but not brown, adipose tissue,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 22, pp. 12532–12537, 2001.
View at: Publisher Site | Google Scholar
M. C. Carmona, R. Iglesias, M.-J. Obregón, G. J. Darlington, F. Villarroya, and M. Giralt, “Mitochondrial biogenesis and thyroid status maturation in brown fat require CCAAT/enhancer-binding protein $α$ ,” Journal of Biological Chemistry, vol. 277, no. 24, pp. 21489–21498, 2002.
View at: Publisher Site | Google Scholar
Z. Wu, E. D. Rosen, R. Brun et al., “Cross-regulation of C/EBP $a$ and PPAR $?$ controls the transcriptional pathway of adipogenesis and insulin sensitivity,” Molecular Cell, vol. 3, no. 2, pp. 151–158, 1999.
View at: Publisher Site | Google Scholar
P. Yubero, C. Manchado, A.-M. Cassard-Doulcier et al., “CCAAT/enhancer binding proteins $a$ and $ß$ are transcriptional activators of the brown fat uncoupling protein gene promoter,” Biochemical and Biophysical Research Communications, vol. 198, no. 2, pp. 653–659, 1994.
View at: Publisher Site | Google Scholar
M. C. Carmona, E. Hondares, M. L. Rodriguez de la Concepcion et al., “Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBP $ß$ ,” Biochemical Journal, vol. 389, no. 1, pp. 47–56, 2005.
View at: Publisher Site | Google Scholar
I. B. Sears, M. A. MacGinnitie, L. G. Kovacs, and R. A. Graves, “Differentiation-dependent expression of the brown adipocyte uncoupling protein gene: regulation by peroxisome proliferator-activated receptor $γ$ ,” Molecular and Cellular Biology, vol. 16, no. 7, pp. 3410–3419, 1996.
View at: Google Scholar
D. Ricquier and F. Bouillaud, “The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP,” Biochemical Journal, vol. 345, no. 2, pp. 161–179, 2000.
View at: Publisher Site | Google Scholar
U. C. Kozak, J. Kopecky, J. Teisinger, S. Enerback, B. Boyer, and L. P. Kozak, “An upstream enhancer regulating brown-fat-specific expression of the mitochondrial uncoupling protein gene,” Molecular and Cellular Biology, vol. 14, no. 1, pp. 59–67, 1994.
View at: Google Scholar
P. Yubero, M. J. Barberá, R. Alvarez et al., “Dominant negative regulation by c-Jun of transcription of the uncoupling protein-1 gene through a proximal cAMP-regulatory element: a mechanism for repressing basal and norepinephrine-induced expression of the gene before brown adipocyte differentiation,” Molecular Endocrinology, vol. 12, no. 7, pp. 1023–1037, 1998.
View at: Publisher Site | Google Scholar
A.-M. Cassard-Doulcier, C. Gelly, N. Fox et al., “Tissue-specific and $ß$ -adrenergic regulation of the mitochondrial uncoupling protein gene: control by cis-acting elements in the $5^{'}$ -flanking region,” Molecular Endocrinology, vol. 7, no. 4, pp. 497–506, 1993.
View at: Publisher Site | Google Scholar
R. Alvarez, J. de Andres, P. Yubero et al., “A novel regulatory pathway of brown fat thermogenesis. Retinoic acid is a transcriptional activator of the mitochondrial uncoupling protein gene,” Journal of Biological Chemistry, vol. 270, no. 10, pp. 5666–5673, 1995.
View at: Publisher Site | Google Scholar
R. Rabelo, C. Reyes, A. Schifman, and J. E. Silva, “Interactions among receptors, thyroid hormone response elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone,” Endocrinology, vol. 137, no. 8, pp. 3478–3487, 1996.
View at: Publisher Site | Google Scholar
M. del Mar Gonzalez-Barroso, C. Pecqueur, C. Gelly et al., “Transcriptional activation of the human ucp1 gene in a rodent cell line. Synergism of retinoids, isoproterenol, and thiazolidinedione is mediated by a multipartite response element,” Journal of Biological Chemistry, vol. 275, no. 41, pp. 31722–31732, 2000.
View at: Publisher Site | Google Scholar
M. J. Barberá, A. Schlüter, N. Pedraza, R. Iglesias, F. Villarroya, and M. Giralt, “Peroxisome proliferator-activated receptor α activates transcription of the brown fat uncoupling protein-1 gene. A link between regulation of the thermogenic and lipid oxidation pathways in the brown fat cell,” Journal of Biological Chemistry, vol. 276, no. 2, pp. 1486–1493, 2001.
View at: Publisher Site | Google Scholar
W. Cao, K. W. Daniel, J. Robidoux et al., “p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene,” Molecular and Cellular Biology, vol. 24, no. 7, pp. 3057–3067, 2004.
View at: Publisher Site | Google Scholar
P. Puigserver, Z. Wu, C. W. Park, R. Graves, M. Wright, and B. M. Spiegelman, “A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis,” Cell, vol. 92, no. 6, pp. 829–839, 1998.
View at: Publisher Site | Google Scholar
Z. Wu, P. Puigserver, U. Andersson et al., “Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1,” Cell, vol. 98, no. 1, pp. 115–124, 1999.
View at: Publisher Site | Google Scholar
C. Tiraby, G. Tavernier, C. Lefort et al., “Acquirement of brown fat cell features by human white adipocytes,” Journal of Biological Chemistry, vol. 278, no. 35, pp. 33370–33376, 2003.
View at: Publisher Site | Google Scholar
M. Uldry, W. Yang, J. St-Pierre, J. Lin, P. Seale, and B. M. Spiegelman, “Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation,” Cell Metabolism, vol. 3, no. 5, pp. 333–341, 2006.
View at: Publisher Site | Google Scholar
L. Wilson-Fritch, S. Nicoloro, M. Chouinard et al., “Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone,” The Journal of Clinical Investigation, vol. 114, no. 9, pp. 1281–1289, 2004.
View at: Publisher Site | Google Scholar
E. Hondares, O. Mora, P. Yubero et al., “Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1 $a$ gene transcription: an autoregulatory loop controls PGC-1 $a$ expression in adipocytes via peroxisome proliferator-activated receptor- $?$ coactivation,” Endocrinology, vol. 147, no. 6, pp. 2829–2838, 2006.
View at: Publisher Site | Google Scholar
J. Nedergaard, N. Petrovic, E. M. Lindgren, A. Jacobsson, and B. Cannon, “PPAR $γ$ in the control of brown adipocyte differentiation,” Biochimica et Biophysica Acta, vol. 1740, no. 2, pp. 293–304, 2005.
View at: Google Scholar
L. J. Kelly, P. P. Vicario, G. M. Thompson et al., “Peroxisome proliferator-activated receptors $?$ and $a$ mediate in vivo regulation of uncoupling protein (UCP-1, UCP-2, UCP-3) gene expression,” Endocrinology, vol. 139, no. 12, pp. 4920–4927, 1998.
View at: Publisher Site | Google Scholar
N. Pedraza, G. Solanes, R. Iglesias, M. Vazquez, M. Giralt, and F. Villarroya, “Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice,” Biochemical Journal, vol. 355, no. pt 1, pp. 105–111, 2001.
View at: Publisher Site | Google Scholar
S. Kersten, J. Seydoux, J. M. Peters, F. J. Gonzalez, B. Desvergne, and W. Wahli, “Peroxisome proliferator-activated receptor $α$ mediates the adaptive response to fasting,” Journal of Clinical Investigation, vol. 103, no. 11, pp. 1489–1498, 1999.
View at: Google Scholar
B. Xue, A. Coulter, J. S. Rim, R. A. Koza, and L. P. Kozak, “Transcriptional synergy and the regulation of Ucp1 during brown adipocyte induction in white fat depots,” Molecular and Cellular Biology, vol. 25, no. 18, pp. 8311–8322, 2005.
View at: Publisher Site | Google Scholar
D. G. Nicholls, S. A. Cunningham, and E. Rial, “The bioenergetic mechanisms of brown adipose tissue mitochondria,” in Brown Adipose Tissue, P. Trayhurn and D. G. Nicholls, Eds., pp. 52–85, Edward Arnold, London, UK, 1986.
View at: Google Scholar
Y. X. Wang, C. H. Lee, S. Tiep et al., “Peroxisome-proliferator-activated receptor $d$ activates fat metabolism to prevent obesity,” Cell, vol. 113, no. 2, pp. 159–170, 2003.
View at: Publisher Site | Google Scholar
F. Villarroya, M. Giralt, and R. Iglesias, “Retinoids and adipose tissues: metabolism, cell differentiation and gene expression,” International Journal of Obesity and Related Metabolic Disorders, vol. 23, no. 1, pp. 1–6, 1999.
View at: Publisher Site | Google Scholar
F. Villarroya, R. Iglesias, and M. Giralt, “Retinoids and retinoid receptors in the control of energy balance: novel pharmacological strategies in obesity and diabetes,” Current Medicinal Chemistry, vol. 11, no. 6, pp. 795–805, 2004.
View at: Publisher Site | Google Scholar
A. Chawla and M. A. Lazar, “Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 5, pp. 1786–1790, 1994.
View at: Publisher Site | Google Scholar
P. Puigserver, F. Vazquez, M. L. Bonet, C. Pico, and A. Palou, “In vitro and in vivo induction of brown adipocyte uncoupling protein (thermogenin) by retinoic acid,” Biochemical Journal, vol. 317, no. pt 3, pp. 827–833, 1996.
View at: Google Scholar
M. V. Kumar, G. D. Sunvold, and P. J. Scarpace, “Dietary vitamin A supplementation in rats: suppression of leptin and induction of UCP1 mRNA,” Journal of Lipid Research, vol. 40, no. 5, pp. 824–829, 1999.
View at: Google Scholar
M. L. Bonet, J. Oliver, C. Pico et al., “Opposite effects of feeding a vitamin A-deficient diet and retinoic acid treatment on brown adipose tissue uncoupling protein 1 (UCP1), UCP2 and leptin expression,” Journal of Endocrinology, vol. 166, no. 3, pp. 511–517, 2000.
View at: Publisher Site | Google Scholar
R. Alvarez, M. Checa, S. Brun et al., “Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids,” Biochemical Journal, vol. 345, no. pt 1, pp. 91–97, 2000.
View at: Publisher Site | Google Scholar
S. Kitareewan, L. T. Burka, K. B. Tomer et al., “Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR,” Molecular Biology of the Cell, vol. 7, no. 8, pp. 1153–1166, 1996.
View at: Google Scholar
P. Ellinghaus, C. Wolfrum, G. Assmann, F. Spener, and U. Seedorf, “Phytanic acid activates the peroxisome proliferator-activated receptor $α$ (PPAR $α$ ) in sterol carrier protein 2-/ sterol carrier protein x-deficient mice,” Journal of Biological Chemistry, vol. 274, no. 5, pp. 2766–2772, 1999.
View at: Publisher Site | Google Scholar
A. Schluter, M. J. Barberá, R. Iglesias, M. Giralt, and F. Villarroya, “Phytanic acid, a novel activator of uncoupling protein-1 gene transcription and brown adipocyte differentiation,” Biochemical Journal, vol. 362, no. pt 1, pp. 61–69, 2002.
View at: Publisher Site | Google Scholar
A. Schluter, M. Giralt, R. Iglesias, and F. Villarroya, “Phytanic acid, but not pristanic acid, mediates the positive effects of phytol derivatives on brown adipocyte differentiation,” FEBS Letters, vol. 517, no. 1–3, pp. 83–86, 2002.
View at: Google Scholar
F. Bouillaud, F. Villarroya, E. Hentz, S. Raimbault, A. M. Cassard, and D. Ricquier, “Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a human genomic probe,” Clinical Science, vol. 75, no. 1, pp. 21–27, 1988.
View at: Google Scholar
M. L. Rodriguez de la Concepcion, J. C. Domingo, P. Domingo, M. Giralt, and F. Villarroya, “Uncoupling protein 1 gene expression implicates brown adipocytes in highly active antiretroviral therapy-associated lipomatosis,” AIDS, vol. 18, no. 6, pp. 959–960, 2004.
View at: Publisher Site | Google Scholar
D. S. Weigle, L. E. Selfridge, M. W. Schwartz et al., “Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fasting,” Diabetes, vol. 47, no. 2, pp. 298–302, 1998.
View at: Google Scholar
S. Brun, M. C. Carmona, T. Mampel et al., “Uncoupling protein-3 gene expression in skeletal muscle during development is regulated by nutritional factors that alter circulating non-esterified fatty acids,” FEBS Letters, vol. 453, no. 1-2, pp. 205–209, 1999.
View at: Publisher Site | Google Scholar
P. Schrauwen, M. K. Hesselink, I. Vaartjes et al., “Effect of acute exercise on uncoupling protein 3 is a fat metabolism-mediated effect,” American Journal of Physiology. Endocrinology and Metabolism, vol. 282, no. 1, pp. E11–E17, 2002.
View at: Google Scholar
C. J. Chou, M. C. Cha, D. W. Jung, C. N. Boozer, S. A. Hashim, and F. X. Pi-Sunyer, “High-fat diet feeding elevates skeletal muscle uncoupling protein 3 levels but not its activity in rats,” Obesity Research, vol. 9, no. 5, pp. 313–319, 2001.
View at: Google Scholar
S. Brun, M. C. Carmona, T. Mampel et al., “Activators of peroxisome proliferator-activated receptor- $a$ induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth,” Diabetes, vol. 48, no. 6, pp. 1217–1222, 1999.
View at: Google Scholar
N. Pedraza, G. Solanes, M. C. Carmona et al., “Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene,” Diabetes, vol. 49, no. 7, pp. 1224–1230, 2000.
View at: Google Scholar
O. Boss, E. Bobbioni-Harsch, F. Assimacopoulos-Jeannet et al., “Uncoupling protein-3 expression in skeletal muscle and free fatty acids in obesity,” Lancet, vol. 351, no. 9120, p. 1933, 1998.
View at: Publisher Site | Google Scholar
A. J. Murray, R. E. Anderson, G. C. Watson, G. K. Radda, and K. Clarke, “Uncoupling proteins in human heart,” Lancet, vol. 364, no. 9447, pp. 1786–1788, 2004.
View at: Publisher Site | Google Scholar
D. Kratky, J. G. Strauss, and R. Zechner, “Tissue-specific activity of lipoprotein lipase in skeletal muscle regulates the expression of uncoupling protein 3 in transgenic mouse models,” Biochemical Journal, vol. 355, no. pt 3, pp. 647–652, 2001.
View at: Google Scholar
A. Cabrero, M. Alegret, R. Sanchez, T. Adzet, J. C. Laguna, and M. Vazquez, “Uncoupling protein-3 mRNA up-regulation in C2C12 myotubes after etomoxir treatment,” Biochimica et Biophysica Acta, vol. 1532, no. 3, pp. 195–202, 2001.
View at: Google Scholar
M. E. Young, S. Patil, J. Ying et al., “Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor ( $a$ ) in the adult rodent heart,” FASEB Journal, vol. 15, no. 3, pp. 833–845, 2001.
View at: Publisher Site | Google Scholar
D. M. Muoio, P. S. MacLean, D. B. Lang et al., “Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) $a$ knock-out mice. Evidence for compensatory regulation by PPAR $d$ ,” Journal of Biological Chemistry, vol. 277, no. 29, pp. 26089–26097, 2002.
View at: Publisher Site | Google Scholar
A. J. Murray, M. Panagia, D. Hauton, G. F. Gibbons, and K. Clarke, “Plasma free fatty acids and peroxisome proliferator-activated receptor $α$ in the control of myocardial uncoupling protein levels,” Diabetes, vol. 54, no. 12, pp. 3496–3502, 2005.
View at: Google Scholar
N. Pedraza, M. Rosell, J. Villarroya et al., “Developmental and tissue-specific involvement of PPAR $a$ in the control of mouse uncoupling protein-3 gene expression,” Endocrinology, vol. 147, no. 10, pp. 4695–704, 2006.
View at: Publisher Site | Google Scholar
B. N. Finck, J. J. Lehman, T. C. Leone et al., “The cardiac phenotype induced by PPAR $a$ overexpression mimics that caused by diabetes mellitus,” Journal of Clinical Investigation, vol. 109, no. 1, pp. 121–130, 2002.
View at: Publisher Site | Google Scholar
B. N. Finck, C. Bernal-Mizrachi, D. H. Han et al., “A potential link between muscle peroxisome proliferator-activated receptor- $a$ signaling and obesity-related diabetes,” Cell Metabolism, vol. 1, no. 2, pp. 133–144, 2005.
View at: Publisher Site | Google Scholar
A. Cabrero, G. Llaverias, N. Roglans et al., “Uncoupling protein-3 mRNA levels are increased in white adipose tissue and skeletal muscle of bezafibrate-treated rats,” Biochemical and Biophysical Research Communications, vol. 260, no. 2, pp. 547–556, 1999.
View at: Publisher Site | Google Scholar
G. Solanes, N. Pedraza, R. Iglesias, M. Giralt, and F. Villarroya, “The human uncoupling protein-3 gene promoter requires MyoD and is induced by retinoic acid in muscle cells,” FASEB Journal, vol. 14, no. 14, pp. 2141–2143, 2000.
View at: Publisher Site | Google Scholar
I. Nagase, S. Yoshida, X. Canas et al., “Up-regulation of uncoupling protein 3 by thyroid hormone, peroxisome proliferator-activated receptor ligands and 9-cis retinoic acid in L6 myotubes,” FEBS Letters, vol. 461, no. 3, pp. 319–322, 1999.
View at: Publisher Site | Google Scholar
C. Son, K. Hosoda, J. Matsuda et al., “Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for PPARs in L6 myotubes,” Endocrinology, vol. 142, no. 10, pp. 4189–4194, 2001.
View at: Publisher Site | Google Scholar
I. Lopez-Solache, V. Marie, E. Vignault, A. Camirand, and J. E. Silva, “Regulation of uncoupling protein-2 mRNA in L6 myotubules: I: thiazolidinediones stimulate uncoupling protein-2 gene expression by a mechanism requiring ongoing protein synthesis and an active mitogen-activated protein kinase,” Endocrine, vol. 19, no. 2, pp. 197–208, 2002.
View at: Publisher Site | Google Scholar
Y. X. Wang, C. L. Zhang, R. T. Yu et al., “Regulation of muscle fiber type and running endurance by PPAR $d$ ,” PLoS Biology, vol. 2, no. 10, p. e294, 2004.
View at: Publisher Site | Google Scholar
S. Luquet, J. Lopez-Soriano, D. Holst et al., “Peroxisome proliferator-activated receptor $d$ controls muscle development and oxidative capability,” FASEB Journal, vol. 17, no. 15, pp. 2299–2301, 2003.
View at: Publisher Site | Google Scholar
L. Cheng, G. Ding, Q. Qin et al., “Cardiomyocyte-restricted peroxisome proliferator-activated receptor- $d$ deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy,” Nature Medicine, vol. 10, no. 11, pp. 1245–1250, 2004.
View at: Publisher Site | Google Scholar
U. Dressel, T. L. Allen, J. B. Pippal, P. R. Rohde, P. Lau, and G. E. Muscat, “The peroxisome proliferator-activated receptor $β$ / $δ$ agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells,” Molecular Endocrinology, vol. 17, no. 12, pp. 2477–2493, 2003.
View at: Publisher Site | Google Scholar
T. Tanaka, J. Yamamoto, S. Iwasaki et al., “Activation of peroxisome proliferator-activated receptor $d$ induces fatty acid $ß$ -oxidation in skeletal muscle and attenuates metabolic syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 15924–15929, 2003.
View at: Publisher Site | Google Scholar
G. Solanes, N. Pedraza, R. Iglesias, M. Giralt, and F. Villarroya, “Functional relationship between MyoD and peroxisome proliferator-activated receptor-dependent regulatory pathways in the control of the human uncoupling protein-3 gene transcription,” Molecular Endocrinology, vol. 17, no. 10, pp. 1944–1958, 2003.
View at: Google Scholar
F. Felipe, M. L. Bonet, J. Ribot, and A. Palou, “Up-regulation of muscle uncoupling protein 3 gene expression in mice following high fat diet, dietary vitamin A supplementation and acute retinoic acid-treatment,” International Journal of Obesity and Related Metabolic Disorders, vol. 27, no. 1, pp. 60–69, 2003.
View at: Publisher Site | Google Scholar
F. Villarroya, “Mitochondrial uncoupling protein-3: beyond thermoregulation,” in Recent Research Developments in Biochemistry, S. Pandalai, Ed., vol. 3, pp. 691–704, Research Signpost, Kerala, India, 2002.
View at: Google Scholar
P. Schrauwen, J. Xia, K. Walder, S. Snitker, and E. Ravussin, “A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male non-diabetic Pima Indians,” International Journal of Obesity and Related Metabolic Disorders, vol. 23, no. 12, pp. 1242–1245, 1999.
View at: Publisher Site | Google Scholar
A. Cabrero, M. Alegret, R. M. Sanchez, T. Adzet, J. C. Laguna, and M. Vazquez, “Down-regulation of uncoupling protein-3 and -2 by thiazolidinediones in C2C12 myotubes,” FEBS Letters, vol. 484, no. 1, pp. 37–42, 2000.
View at: Publisher Site | Google Scholar
C. S. Hwang and M. D. Lane, “Up-regulation of uncoupling protein-3 by fatty acid in C2C12 myotubes,” Biochemical and Biophysical Research Communications, vol. 258, no. 2, pp. 464–469, 1999.
View at: Publisher Site | Google Scholar
T. Shimokawa, M. Kato, Y. Watanabe et al., “In vivo effects of pioglitazone on uncoupling protein-2 and -3 mRNA levels in skeletal muscle of hyperglycemic KK mice,” Biochemical and Biophysical Research Communications, vol. 251, no. 1, pp. 374–378, 1998.
View at: Publisher Site | Google Scholar
B. Brunmair, F. Gras, L. Wagner et al., “Expression of uncoupling protein-3 mRNA in rat skeletal muscle is acutely stimulated by thiazolidinediones: an exercise-like effect?” Diabetologia, vol. 47, no. 9, pp. 1611–1614, 2004.
View at: Publisher Site | Google Scholar
A. L. Hevener, W. He, Y. Barak et al., “Muscle-specific Pparg deletion causes insulin resistance,” Nature Medicine, vol. 9, no. 12, pp. 1491–1497, 2003.
View at: Publisher Site | Google Scholar
E. Chevillotte, J. Rieusset, M. Roques, M. Desage, and H. Vidal, “The regulation of uncoupling protein-2 gene expression by $ω$ -6 polyunsaturated fatty acids in human skeletal muscle cells involves multiple pathways, including the nuclear receptor peroxisome proliferator-activated receptor $β$ ,” Journal of Biological Chemistry, vol. 276, no. 14, pp. 10853–10860, 2001.
View at: Publisher Site | Google Scholar
A. V. Medvedev, S. K. Snedden, S. Raimbault, D. Ricquier, and S. Collins, “Transcriptional regulation of the mouse uncoupling protein-2 gene,” Journal of Biological Chemistry, vol. 276, no. 14, pp. 10817–10823, 2001.
View at: Publisher Site | Google Scholar
J. Matsuda, K. Hosoda, H. Itoh et al., “Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes,” Diabetes, vol. 47, no. 11, pp. 1809–1814, 1998.
View at: Google Scholar
V. Emilsson, J. O'Dowd, S. Wang et al., “The effects of rexinoids and rosiglitazone on body weight and uncoupling protein isoform expression in the Zucker fa/fa rat,” Metabolism, vol. 49, no. 12, pp. 1610–1615, 2000.
View at: Publisher Site | Google Scholar
J. E. Digby, V. E. Crowley, C. P. Sewter, J. P. Whitehead, J. B. Prins, and S. O'Rahilly, “Depot-related and thiazolidinedione-responsive expression of uncoupling protein 2 (UCP2) in human adipocytes,” International Journal of Obesity and Related Metabolic Disorders, vol. 24, no. 5, pp. 585–592, 2000.
View at: Publisher Site | Google Scholar
J. Aubert, O. Champigny, P. Saint-Marc et al., “Up-regulation of UCP-2 gene expression by PPAR agonists in preadipose and adipose cells,” Biochemical and Biophysical Research Communications, vol. 238, no. 2, pp. 606–611, 1997.
View at: Publisher Site | Google Scholar
M. C. Carmona, A. Valmaseda, R. Iglesias et al., “9-cis retinoic acid induces the expression of the uncoupling protein-2 gene in brown adipocytes,” FEBS Letters, vol. 441, no. 3, pp. 447–450, 1998.
View at: Publisher Site | Google Scholar
C. Y. Zhang, G. Baffy, P. Perret et al., “Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, $ß$ cell dysfunction, and type 2 diabetes,” Cell, vol. 105, no. 6, pp. 745–755, 2001.
View at: Publisher Site | Google Scholar
B. B. Lowell and G. I. Shulman, “Mitochondrial dysfunction and type 2 diabetes,” Science, vol. 307, no. 5708, pp. 384–387, 2005.
View at: Publisher Site | Google Scholar
A. V. Medvedev, J. Robidoux, X. Bai et al., “Regulation of the uncoupling protein-2 gene in INS-1 $ß$ -cells by oleic acid,” Journal of Biological Chemistry, vol. 277, no. 45, pp. 42639–42644, 2002.
View at: Publisher Site | Google Scholar
H. Oberkofler, K. Klein, T. K. Felder, F. Krempler, and W. Patsch, “Role of the peroxisome proliferator-activated receptor- $γ$ coactivator-1 $α$ in the transcriptional regulation of the human uncoupling protein 2 gene in INS-1E cells,” Endocrinology, vol. 147, no. 2, pp. 966–976, 2006.
View at: Publisher Site | Google Scholar
Y. T. Zhou, M. Shimabukuro, M. Y. Wang et al., “Role of peroxisome proliferator-activated receptor- $a$ in disease of pancreatic $ß$ cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 15, pp. 8898–8903, 1998.
View at: Publisher Site | Google Scholar
K. Tordjman, K. N. Standley, C. Bernal-Mizrachi et al., “PPAR $a$ suppresses insulin secretion and induces UCP2 in insulinoma cells,” Journal of Lipid Research, vol. 43, no. 6, pp. 936–943, 2002.
View at: Google Scholar
S. Gremlich, C. Nolan, R. Roduit et al., “Pancreatic islet adaptation to fasting is dependent on peroxisome proliferator-activated receptor- $a$ transcriptional upregulation of fatty acid oxidation,” Endocrinology, vol. 146, no. 1, pp. 375–382, 2005.
View at: Publisher Site | Google Scholar
E. Ito, S. Ozawa, K. Takahashi et al., “PPAR- $?$ overexpression selectively suppresses insulin secretory capacity in isolated pancreatic islets through induction of UCP-2 protein,” Biochemical and Biophysical Research Communications, vol. 324, no. 2, pp. 810–814, 2004.
View at: Publisher Site | Google Scholar
J. Tian, G. Li, Y. Gu et al., “Role and mechanism of rosiglitazone on the impairment of insulin secretion induced by free fatty acids on isolated rat islets,” Chinese Medical Journal, vol. 119, no. 7, pp. 574–580, 2006.
View at: Google Scholar
P. Steneberg, N. Rubins, R. Bartoov-Shifman, M. D. Walker, and H. Edlund, “The FFA receptor GRP40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse,” Cell metabolism, vol. 1, no. 4, pp. 245–258, 2005.
View at: Publisher Site | Google Scholar
D. Larrouy, P. Laharrague, G. Carrera et al., “Kupffer cells are a dominant site of uncoupling protein 2 expression in rat liver,” Biochemical and Biophysical Research Communications, vol. 235, no. 3, pp. 760–764, 1997.
View at: Google Scholar
T. Nakatani, N. Tsuboyama-Kasaoka, M. Takahashi, S. Miura, and O. Ezaki, “Mechanism for peroxisome proliferator-activated receptor- $α$ activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes,” Journal of Biological Chemistry, vol. 277, no. 11, pp. 9562–9569, 2002.
View at: Publisher Site | Google Scholar
R. A. Memon, L. H. Tecott, K. Nonogaki et al., “Up-regulation of peroxisome proliferator-activated receptor (PPAR- $a$ ) and PPAR- $?$ messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR- $a$ -responsive adipose tissue-specific genes in the liver of obese diabetic mice,” Endocrinology, vol. 141, no. 11, pp. 4021–4031, 2000.
View at: Publisher Site | Google Scholar
D. Patsouris, J. K. Reddy, M. Muller, and S. Kersten, “Peroxisome proliferator-activated receptor $α$ mediates the effects of high-fat diet on hepatic gene expression,” Endocrinology, vol. 147, no. 3, pp. 1508–1516, 2006.
View at: Publisher Site | Google Scholar
N. Tsuboyama-Kasaoka, M. Takahashi, H. Kim, and O. Ezaki, “Up-regulation of liver uncoupling protein-2 mRNA by either fish oil feeding or fibrate administration in mice,” Biochemical and Biophysical Research Communications, vol. 257, no. 3, pp. 879–885, 1999.
View at: Publisher Site | Google Scholar
M. B. Armstrong and H. C. Towle, “Polyunsaturated fatty acids stimulate hepatic UCP-2 expression via a PPAR $α$ -mediated pathway,” American Journal of Physiology - Endocrinology and Metabolism, vol. 281, no. 6, pp. E1197–E1204, 2001.
View at: Google Scholar
H. J. Grav, K. J. Tronstad, O. A. Gudbrandsen et al., “Changed energy state and increased mitochondrial $ß$ -oxidation rate in liver of rats associated with lowered proton electrochemical potential and stimulated uncoupling protein 2 (UCP-2) expression,” Journal of Biological Chemistry, vol. 278, no. 33, pp. 30525–30533, 2003.
View at: Google Scholar
A. Lanni, F. P. Mancini, L. Sabatino et al., “De novo expression of uncoupling protein 3 is associated to enhanced mitochondrial thioesterase-1 expression and fatty acid metabolism in liver of fenofibrate-treated rats,” FEBS Letters, vol. 525, no. 1–3, pp. 7–12, 2002.
View at: Publisher Site | Google Scholar
E. Silvestri, P. De Lange, M. Moreno et al., “Fenofibrate activates the biochemical pathways and the novo expression of genes related to lipid handling and uncoupling protein-3 functions in liver of normal rats,” Biochimica et Biophysica Acta, vol. 1757, no. 5-6, pp. 486–495, 2006.
View at: Publisher Site | Google Scholar
C. Hurtaud, C. Gelly, F. Bouillaud, and C. Lévi-Meyrueis, “Translation control of UCP2 synthesis by upstream open reading frame,” Cellular and Molecular Life Sciences, vol. 63, no. 15, pp. 1780–1789, 2006.
View at: Publisher Site | Google Scholar
C. Fleury, M. Neverova, S. Collins et al., “Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia,” Nature Genetics, vol. 15, no. 3, pp. 269–272, 1997.
View at: Publisher Site | Google Scholar
A. C. Li and W. Palinski, “Peroxisome proliferators-activated receptors: how their effects in macrophages can lead to the development of new drug therapy against atherosclerosis,” Annual Review of Pharmacology and Toxicology, vol. 46, pp. 1–39, 2006.
View at: Publisher Site | Google Scholar
T. E. Akiyama, S. Sakai, G. Lambert et al., “Conditional disruption of the peroxisome proliferator-activated receptor $?$ gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux,” Molecular and Cellular Biology, vol. 22, no. 8, pp. 2607–2619, 2002.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2007 Francesc Villarroya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation Order printed copies

Views

839

Downloads

1668

Citations