Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-07T08:32:47.064Z Has data issue: false hasContentIssue false
  • English
  • Français

Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in energy metabolism revisited

Published online by Cambridge University Press:  05 March 2007

Patrick Schrauwen  and
Matthijs Hesselink
Patrick Schrauwen*
Affiliation:
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Departments of Human Biology and Movement Sciences, Maastricht University, PO Box 616, 6200, MD, Maastricht, The Netherlands
Matthijs Hesselink
Affiliation:
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Departments of Human Biology and Movement Sciences, Maastricht University, PO Box 616, 6200, MD, Maastricht, The Netherlands
*
*Corresponding author: Dr P. Schrauwen, fax +31 43 3670976, [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Physical activity influences energy metabolism in human subjects by increasing activity-induced energy expenditure and resting metabolic rate for several hours after exercise. On the other hand, physical activity increases mechanical energy efficiency, suggesting that trained subjects would need less energy for daily activities. The underlying mechanism by which physical activity influences energy metabolism is largely unknown. The skeletal muscle-specific homologue of uncoupling protein (UCP) 1, UCP3, could possibly play a major role in energy expenditure. UCP3 is, like UCP1, able to uncouple respiration from ATP production. A strong link or association between the UCP3 gene and energy metabolism was found. Furthermore, UCP3 mRNA expression is related to sleeping metabolic rate, and thyroid hormone, a powerful stimulator of energy expenditure, up regulates UCP3. Finally, mice overexpressing UCP3 are hyperphagic but lean. These findings indicated that UCP3 is related to energy metabolism and that UCP3 could have a role in the effect of physical activity on energy expenditure. Thus, acute exercise up regulates UCP3, whereas endurance training results in the down-regulation of UCP3 protein content. Only a minimal amount of physical activity is needed for down-regulation of UCP3. Moreover, there is very strong evidence that UCP3 is negatively related to mechanical energy efficiency, suggesting that the down-regulation of UCP3 with training increases mechanical energy efficiency. Taken together, although the exact function of UCP3 is still unknown, exercise and training studies clearly show that under certain circumstances UCP3 is strongly related to human energy metabolism, possibly as a secondary effect of its (yet) unknown primary function.

Keywords

Uncoupling protein 3Endurance trainingEnergy expenditure
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 3 , August 2003 , pp. 635 - 643
Copyright
Copyright © The Nutrition Society 2003

References

Astrup, A Bulow, J, Madsen, J & Christensen, NJ (1985) Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. American Journal of Physiology 248, E507–E515.Google ScholarPubMed
Astrup, A, Toubro, S, Dalgaard, LT, Urhammer, SA, Sørensen, TIA & Pedersen, O (1999) Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-h energy expenditure and substrate oxidation. International Journal of Obesity and Related Metabolic Disorders 23, 1030–1034.CrossRefGoogle Scholar
Bahr, R, Ingnes, I, Vaage, O, Sejersted, OM & Newsholme, EA (1987) Effect of duration of exercise on excess postexercise O2 consumption. Journal of Applied Physiology 62, 485–490.CrossRefGoogle ScholarPubMed
Bielinski, R, Schutz, Y & Jéquier, E (1985) Energy metabolism during the postexercise recovery in man. American Journal of Clinical Nutrition 42, 69–82.CrossRefGoogle ScholarPubMed
Boss, O, Samec, S, Desplanches, D, Mayet, M-H, Seydoux, J, Muzzin, P & Giacobino, J-P (1998a) Effect of endurance training on mRNA expression of uncoupling proteins 1, 2 and 3 in the rat. FASEB Journal 12, 335–339.CrossRefGoogle Scholar
Boss, O, Samec, S, Kühne, F, Bijlenga, P, Assimacopoulos-Jeannet, F, Seydoux, J, Giacobino, J-P & Muzzin, P (1998b) Uncoupling protein-3 expression in rodent skeletal muscle is modulated by Physical activity, energy expenditure, obesity 641 food intake but not by changes in environmental temperature. Journal of Biological Chemistry 273, 5–8.CrossRefGoogle Scholar
Boss, O, Samec, S, Paoloni-Giacobino, A, Rossier, C, Dulloo, A, Seydoux, J, Muzzin, P & Giacobino, J-P (1997) Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Letters 408, 39–42.CrossRefGoogle ScholarPubMed
Bouchard, C, Pérusse, L, Chagnon, YC, Warden, G & Ricquier, D (1997) Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans. Human Molecular Genetics 6, 1887–1889.CrossRefGoogle ScholarPubMed
Broeder, CE, Burrhus, KA, Svanevik, LS & Wilmore, JH (1992) The effects of either high-intensity resistance or endurance training on resting metabolic rate. American Journal of Clinical Nutrition 55, 802–810.CrossRefGoogle ScholarPubMed
Buemann, B, Schierning, B, Toubro, S, Bibby, B, Sorensen, T, Dalgaard, L, Pedersen, O & Astrup, A (2001) The association between the val/ala-55 polymorphism of the uncoupling protein 2 gene and exercise efficiency. International Journal of Obesity and Related Metabolic Disorders 25, 467–471.CrossRefGoogle ScholarPubMed
Clapham, JC, Arch, JR, Chapman, H, Haynes, A, Lister, C, Moore, GB et al. (2000) Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406, 415–418.CrossRefGoogle ScholarPubMed
Cline, GW, Vidal-Puig, AJ, Dufour, S, Cadman, KS, Lowell, BB & Shulman, GI (2001) In vivo effects of uncoupling protein-3 gene disruption on mitochondrial energy metabolism. Journal of Biological Chemistry 276, 20240–20244.CrossRefGoogle ScholarPubMed
Cortright, RN, Zheng, D, Jones, JP, Fluckey, JD, DiCarlo, SE, Grujic, D, Lowell, BB & Dohm, GL (1999) Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation. American Journal of Physiology 276, E217–E221.Google ScholarPubMed
Curtin, NA, Clapham, JC & Barclay, CJ, (2002) Excess recovery heat production by isolated muscles from mice overexpressing uncoupling protein-3. Journal of Physiology 542, 231–235.CrossRefGoogle ScholarPubMed
Davis, JR, Tagliaferro, AR, Kertzer, R, Gerardo, T, Nichols, J & Wheeler, J (1983) Variations in dietary-induced thermogenesis and body fatness with aerobic capacity. European Journal of Applied Physiology and Occupational Physiology 50, 319–329.CrossRefGoogle ScholarPubMed
de Lange, P, Lanni, A, Beneduce, L, Moreno, M, Lombardi, A, Silvestri, E & Goglia, F (2001) Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology 142, 3414–3420.CrossRefGoogle ScholarPubMed
Dulloo, AG & Samec, S (2001) Uncoupling proteins: their roles in adaptive thermogenesis and substrate metabolism reconsidered. British Journal of Nutrition 86, 123–139.CrossRefGoogle ScholarPubMed
Fleury, C, Neverova, M, Collins, S, Raimbault, S, Champigny, O, Levi-Meyrueis, C, Bouillaud, F, Seldin, MF, Surwit, RS, Ricquier, D & Warden, CH (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nature Genetics 15, 269–273.CrossRefGoogle ScholarPubMed
Fontaine, E, Savard, R, Tremblay, A, Despres, JP, Poehlman, E & Bouchard, C (1985) Resting metabolic rate in monozygotic and dizygotic twins. Acta Geneticae Medicae et Gemellologiae 34, 41–47.CrossRefGoogle ScholarPubMed
Freyschuss, U & Melcher, A (1978) Exercise energy expenditure in extreme obesity: influence of ergometry type and weight loss. Scandinavian Journal of Clinical and Laboratory Investigation 38, 753–759.CrossRefGoogle ScholarPubMed
Gaesser, GA & Brooks, GA (1975) Muscular efficiency during steady-state exercise: effects of speed and work rate. Journal of Applied Physiology 38, 1132–1139.CrossRefGoogle Scholar
Gimeno, RE, Dembski, M, Weng, X, Deng, N, Shyjan, AW, Gimeno, CJ, Iris, F, Ellis, SJ, Woolf, EA & Tartaglia, LA (1997) Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis. Diabetes 46, 900–906.CrossRefGoogle ScholarPubMed
Gissane, C, Corrigan, DL & White, JA (1991) Gross efficiency responses to exercise conditioning in adult males of various ages. Journal of Sports Sciences 9, 383–391.CrossRefGoogle ScholarPubMed
Gong, D-W, He, Y, Karas, M & Reitman, M (1997) Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, ß3-adrenergic agonists, and leptin. Journal of Biological Chemistry 272, 24129–24132.CrossRefGoogle Scholar
Gong, DW, Monemdjou, S, Gavrilova, O, Leon, LR, Marcus-Samuels, B, Chou, CJ, Everett, C, Kozak, LP, Li, C, Deng, C, Harper, ME & Reitman, ML (2000) Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. Journal of Biological Chemistry 275, 16251–16257.CrossRefGoogle ScholarPubMed
Hagen, T & Vidal-Puig, A (2002) Mitochondrial uncoupling proteins in human physiology and disease. Minerva Medica 93, 41–57.Google ScholarPubMed
Herring, JL, Mole, PA, Meredith, CN & Stern, JS (1992) Effect of suspending exercise training on resting metabolic rate in women. Medicine and Science in Sports and Exercise 24, 59–65.CrossRefGoogle ScholarPubMed
Hjeltnes, N, Fernström, M, Zierath, JR & Krook, A (1999) Regulation of UCP2 and UCP3 by muscle disuse and physical activity in tetraplegic subjects. Diabetologia 42, 826–830.CrossRefGoogle ScholarPubMed
Khalfallah, Y, Fages, S, Laville, M, Langin, D & Vidal, H, (2000) Regulation of uncoupling protein-2 and uncoupling protein-3 mRNA expression during lipid infusion in human skeletal muscle and subcutaneous adipose tissue. Diabetes 49, 25–31.CrossRefGoogle ScholarPubMed
Kimm, SY, Glynn, NW, Aston, CE, Damcott, CM, Poehlman, ET, Daniels, SR & Ferrell, RE (2002) Racial differences in the relation between uncoupling protein genes and resting energy expenditure. American Journal of Clinical Nutrition 75, 714–719.CrossRefGoogle ScholarPubMed
Klannemark, M, Orho, M & Groop, L (1998) No relationship between identified variants in the uncoupling protein 2 gene and energy expenditure. European Journal of Endocrinology 139, 217–223.CrossRefGoogle ScholarPubMed
Lammert, O, Hansen, ES (1982) Effects of excessive caloric intake and caloric restriction on body weight and energy expenditure at rest and light exercise. Acta Physiologica Scandinavica 114, 135–141.CrossRefGoogle ScholarPubMed
Lanouette, CM, Giacobino, JP, Perusse, L, Lacaille, M, Yvon, C, Chagnon, M, Kuhne, F, Bouchard, C, Muzzin, P & Chagnon, YC (2001) Association between uncoupling protein 3 gene and obesity-related phenotypes in the Quebec Family Study. Molecular Medicine 7, 433–441.CrossRefGoogle ScholarPubMed
Lebon, V, Dufour, S, Petersen, KF, Ren, J, Jucker, BM, Slezak, LA, Cline, GW, Rothman, DL & Shulman, GI (2001) Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. Journal of Clinical Investigation 108, 733–737.CrossRefGoogle ScholarPubMed
Lentes, K-U, Tu, N, Chen, H, Winnikes, U, Reinert, I, Marmann, G & Pirke, KM (1999) Genomic organization and mutational analysis of the human UCP2 gene, a prime candidate gene for human obesity. Journal of Receptor and Signal Transduction Research 19, 229–244.CrossRefGoogle ScholarPubMed
Meijer, GA, Westerterp, KR, Seyts, GH, Janssen, GM, Saris, WH & ten Hoor, F (1991) Body composition and sleeping metabolic rate in response to a 5-month endurance-training programme in adults. European Journal of Applied Physiology and Occupational Physiology 62, 18–21.CrossRefGoogle ScholarPubMed
Millet, L, Vidal, H, Andreelli, F, Larrouy, D, Riou, J-P, Ricquier, D, Laville, M & Langin, D (1997) Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans. Journal of Clinical Investigation 100, 2665–2670.CrossRefGoogle ScholarPubMed
Mitchell, P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation Biological Reviews of the Cambridge Philosophical Society 41, 445–502.CrossRefGoogle ScholarPubMed
Nicholls, DG & Locke, RM (1984) Thermogenic mechanisms in brown fat. Physiological Reviews 64, 1–64.CrossRefGoogle ScholarPubMed
Pedersen, SB, Lund, S, Buhl, ES & Richelsen, B (2001) Insulin and contraction directly stimulate UCP2 and UCP3 mRNA expression in rat skeletal muscle in vitro. Biochemical and Biophysical Research Communications 283, 19–25.CrossRefGoogle ScholarPubMed
Pilegaard, H, Keller, C, Steensberg, A, Helge, JW, Pedersen, BK, Saltin, B & Neufer, PD (2002) Influence of pre-exercise muscle glycogen content on exercise-induced transcriptional regulation of metabolic genes. Journal of Physiology 541, 261–271.CrossRefGoogle ScholarPubMed
Pilegaard, H, Ordway, GA, Saltin, B & Neufer, PD (2000) Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise. American Journal of Physiology 279, E806–E814.Google ScholarPubMed
Poehlman, ET, Gardner, AW, Arciero, PJ, Goran, MI & Calles-Escandon, J (1994) Effects of endurance training on total fat oxidation in elderly persons. Journal of Applied Physiology 76, 2281–2287.CrossRefGoogle ScholarPubMed
Poehlman, ET, Melby, CL, Bradylak, SF & Calles, J (1988) Resting metabolic rate and postprandial thermogenesis in highly trained and untrained males. American Journal of Clinical Nutrition 47, 793–798.CrossRefGoogle ScholarPubMed
Pratley, R, Nicklas, B, Rubin, M, Miller, J, Smith, A, Smith, M, Hurley, B & Goldberg, A (1994) Strength training increases resting metabolic rate and norepinephrine levels in healthy 50- to 65-yr-old men. Journal of Applied Physiology 76, 133–137.CrossRefGoogle ScholarPubMed
Ravussin, E, Lillioja, S, Anderson, TE, Christin, L & Bogardus, C (1986) Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber. Journal of Clinical Investigation 78, 1568–1578.CrossRefGoogle ScholarPubMed
Ravussin, E, Lillioja, S, Knowler, WC, Christen, L, Freymond, D, Abbott, WGH, Boyce, V, Howard, BV & Bogardus, C (1988) Reduced rate of energy expenditure as a risk factor for bodyweight gain New England Journal of Medicine 318, 467–472.CrossRefGoogle Scholar
Ruderman, NB, Saha, AK, Vavvas, D & Witters, LA (1999) Malonyl-CoA, fuel sensing, and insulin resistance American Journal of Physiology 276, E1–E18.Google ScholarPubMed
Russell, A, Wadley, G, Snow, R, Giacobino, JP, Muzzin, P, Garnham, A & Cameron-Smith, D (2002) Slow component of [V]O(2)kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity. International Journal of Obesity and Related Metabolic Disorders 26, 157–164.CrossRefGoogle Scholar
Russell, AP, Wadley, G, Hesselink, MKC, Schaart, G, Lo, SK, Léger, B, Garnham, A, Kornips, E, Cameron-Smith, D, Giacobino, JP, Muzzin, P, Snow, R & Schrauwen, P (2003) UCP3 protein expression is lower in type I, IIa and IIx muscle fiber types of endurance trained compared to untrained subjects European Journal of Physiology 445, 563–569.CrossRefGoogle ScholarPubMed
Schrauwen, P & Hesselink, MKC (2002) UCP2 and UCP3 in muscle controlling body metabolism. Journal of Experimental Biology 205, 2275–2285.CrossRefGoogle ScholarPubMed
Schrauwen, P, Hesselink, MK, Vaartjes, I, Kornips, E, Saris, WH, Giacobino, JP & Russell, A (2002 a) Effect of acute exercise on uncoupling protein 3 is a fat metabolism-mediated effect. American Journal of Physiology 282, E11–17.Google ScholarPubMed
Schrauwen, P, Saris, WH & Hesselink, MK (2001) An alternative function for human uncoupling protein 3: protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix. FASEB Journal 15, 2497–2502.CrossRefGoogle ScholarPubMed
Schrauwen, P, Schaart, G, Saris, WH, Slieker, LJ, Glatz, JF, Vidal, H & Blaak, EE (2000) The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects. Diabetologia 43, 1408–1416.CrossRefGoogle ScholarPubMed
Schrauwen, P, Troost, FJ, Xia, J, Ravussin, E & Saris, WH (1999a) Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects. International Journal of Obesity and Related Metabolic Disorders 23, 966–972.CrossRefGoogle ScholarPubMed
Schrauwen, P, Van Aggel-Leijssen, DP, Hul, G, Wagenmakers, AJ, Vidal, H, Saris, WH & Van Baak, MA (2002 b) The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-CoA carboxylase-2 expression. Diabetes 51, 2220–2226.CrossRefGoogle ScholarPubMed
Schrauwen, P & Westerterp, KR (2000) The role of high-fat diets and physical activity in the regulation of body weight. British Journal of Nutrition 84, 417–427.CrossRefGoogle ScholarPubMed
Schrauwen, P, Westerterp-Plantenga, MS, Kornips, E, Schaart, G & van Marken Lichtenbelt, WD (2002c) The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans. International Journal of Obesity and Related Metabolic Disorders 26, 450–457.CrossRefGoogle ScholarPubMed
Schrauwen, P, Xia, J, Bogardus, C, Pratley, RE & Ravussin, E (1999b) Skeletal muscle uncoupling protein 3 expression is a determinant of energy expenditure in Pima Indians. Diabetes 48, 146–149.CrossRefGoogle ScholarPubMed
Schulz, LO, Nyomba, BL, Alger, S, Anderson, TE & Ravussin, E (1991) Effect of endurance training on sedentary energy expenditure measured in a respiratory chamber. American Journal of Physiology 260, E257–E261.Google Scholar
Simonsen, L, Stallknecht, B & Bulow, J (1993) Contribution of skeletal muscle and adipose tissue to adrenaline-induced thermogenesis in man. International Journal of Obesity and Related Metabolic Disorders 17, Suppl. 3, S47–S51, S68.Google ScholarPubMed
Simonyan, RA, Jimenez, M, Ceddia, RB, Giacobino, JP, Muzzin, P & Skulachev, VP (2001) Cold-induced changes in the energy coupling and the UCP3 level in rodent skeletal muscles. Biochimica et Biophysica Acta 1505, 271–279.CrossRefGoogle ScholarPubMed
Skulachev, VP (1998) Uncoupling: new approaches to an old problem of bioenergetics. Biochimica et Biophysica Acta 1363, 100–124.CrossRefGoogle Scholar
Tremblay, A, Fontaine, E, Poehlman, ET, Mitchell, D, Perron, L & Bouchard, C (1986) The effect of exercise-training on resting metabolic rate in lean and obese moderately obese individuals International Journal of Obesity and Related Metabolic Disorders 10, 511–517.Google ScholarPubMed
Tremblay, A, Nadeau, A, Fournier, G & Bouchard, C (1988) Effect of a three-day interruption of exercise-training on resting metabolic rate and glucose-induced thermogenesis in trained individuals. International Journal of Obesity and Related Metabolic Disorders 12, 163–168.Google Scholar
Tsuboyama-Kasaoka, N, Tsunoda, N, Maruyama, K, Takahashi, M, Kim, H, Ikemoto, S & Ezaki, O (1998) Up-regulation of uncoupling protein 3 (UCP3) mRNA by exercise training and down-regulation of UCP3 by denervation in skeletal muscles. Biochemical and Biophysical Research Communications 247, 498–503.CrossRefGoogle ScholarPubMed
Ukkola, O, Tremblay, A, Sun, G, Chagnon, YC & Bouchard, C (2001) Genetic variation at the uncoupling protein 1, 2 and 3 loci and the response to long-term overfeeding. European Journal of Clinical Nutrition 55, 1008–1015.CrossRefGoogle Scholar
Vidal-Puig, A, Rosenbaum, M, Considine, RC, Leibel, RL, Dohm, GL & Lowell, BB (1999) Effects of obesity and stable weight reduction on UCP2 and UCP3 gene expression in humans. Obesity Research 7, 133–140.CrossRefGoogle ScholarPubMed
Vidal-Puig, A, Solanes, G, Grujic, D, Flier, JS & Lowell, BB (1997) UCP3: An uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochemical and Biophysical Research Communications 235, 79–82.CrossRefGoogle ScholarPubMed
Vidal-Puig, AJ, Grujic, D, Zhang, CY, Hagen, T, Boss, O, Ido, Y, Szczepanik, A, Wade, J, Mootha, V, Cortright, R, Muoio, DM & Lowell, BB (2000) Energy metabolism in uncoupling protein 3 gene knockout mice. Journal of Biological Chemistry 275, 16258–16266.CrossRefGoogle ScholarPubMed
Walder, K, Norman, RA, Hanson, RL, Schrauwen, P, Neverova, M, Jenkinson, CP et al. (1998) Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metab olism/obesity in Pima indians. Human Molecular Genetics 7, 1431–1435.CrossRefGoogle Scholar
Westerterp, KR (1998) Alterations in energy balance with exercise. American Journal of Clinical Nutrition 68, 970S–974S.CrossRefGoogle ScholarPubMed
Westerterp, KR, Meijer, GAL, Schoffelen, P & Janssen, E (1994) Body mass, body composition and sleeping metabolic rate before, during and after endurance training. European Journal of Applied Physiology and Occupational Physiology 69, 203–208.CrossRefGoogle ScholarPubMed
Wilmore, JH, Stanforth, PR, Hudspeth, LA, Gagnon, J, Daw, EW, Leon, AS, Rao, DC, Skinner, JS & Bouchard, C (1998) Alterations in resting metabolic rate as a consequence of 20 wk of endurance training: the HERITAGE Family Study. American Journal of Clinical Nutrition 68, 66–71.CrossRefGoogle ScholarPubMed
Yanovski, JA, Diament, AL, Sovik, KN, Nguyen, TT, Li, H, Sebring, NG & Warden, CH (2000) Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children. American Journal of Clinical Nutrition 71, 1405–1420.CrossRefGoogle ScholarPubMed
Zhou, M, Lin, BZ, Coughlin, S, Vallega, G, Pilch, PF (2000) UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase. American Journal of Physiology 279, E622–E629.Google ScholarPubMed