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Effects of leptin on mitochondrial ‘proton leak’ and uncoupling proteins: implications for mammalian energy metabolism

Published online by Cambridge University Press:  28 February 2007

Richard K. Porter*
Affiliation:
Department of Biochemistry, Trinity College Dublin, Dublin 2, Republic of Ireland
J. Fred Andrews
Affiliation:
Department of Physiology, Trinity College Dublin, Dublin 2, Republic of Ireland
*
*Corresponding author: Dr R. K. Porter, fax +353 1 6772400, email rkporter@mail.tcd.ie
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Abstract

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Type
Simposium on ‘Leptin: energy regulation and beyond’
Copyright
Copyright © The Nutrition Society 1998

References

Aubert, J, Champigny, O, Saint-marc, P, Negrel, R, Collins, S, Ricquier, D & Ailhaud, G (1997) Up-regulation of UCP2 gene expression by PPAR agonists in preadipose and adipose cells. Biochemical and Biophysical Research Communications 238, 606611.CrossRefGoogle ScholarPubMed
Blaxter, K (1989) Energy Metabolism in Animals and Man. Cambridge, UK: Cambridge University Press.Google Scholar
Boss, O, Samec, S, Dulloo, A, Seydoux, J, Muzzin, P & Giacobino, JP (1997 a) Tissue-dependent upregulation of rat uncoupling protein-2 expression in response to fasting or cold. FEBS Letters 412, 111114.CrossRefGoogle ScholarPubMed
Boss, O, Samec, S, Kühne, F, Bijlenga, P, Assimacopoulos-jeannet, F, Seydoux, J, Giacobino, J-P & Mizzin, P (1998) Uncoupling protein-3 expression in rodent skeletal muscle is modulated by food intake but not by changes in environmental temperature. Journal of Biological Chemistry 273, 58.CrossRefGoogle Scholar
Boss, O, Samec, S, Paoloni-giacobino, A, Rossier, C, Dulloo, A, Seydoux, J, Muzzin, P & Giacobino, JP (1997 b) Uncoupling protein-3: a new member of the mitochondrial carrier family with tissuespecific expression. FEBS Letters 408, 3942.CrossRefGoogle ScholarPubMed
Bouchard, C, Pérusse, L, Chagnon, YC, Warden, C & 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, 18871889.CrossRefGoogle ScholarPubMed
Brand, MD (1977) The stoichiometric relationships between electron transport, proton translocation and adenosine triphosphate synthesis and hydrolysis in mitochondria. Biochemical Society Transactions 5, 161S1620.CrossRefGoogle Scholar
Brand, MD (1990) The proton leak across the mitochondrial inner membrane. Biochimica et Biophysica Acta 1018, 128133.CrossRefGoogle ScholarPubMed
Brand, MD, Chien, L-F, Ainscow, EK, Rolfe, DFS & Porter, RK (1994) The causes and functions of mitochondrial proton leak. Biochimica et Biophysica Acta 1187, 132139.CrossRefGoogle ScholarPubMed
Brand, MD, Couture, P, Else, PL, Withers, KW & Hulbert, AJ (1991) Evolution of energy metabolism. Biochemical Journal 275, 8186.CrossRefGoogle ScholarPubMed
Brookes, PS, Hulbert, AJ & Brand, MD (1997a) The proton permeability of liposomes made from mitochondrial inner membrane phospholipids: no effect of fatty acid composition. Biochimica et Biophysica Acta 1330, 157164.CrossRefGoogle ScholarPubMed
Brookes, PS, Rolfe, DFS & Brand, MD (1997b) The proton permeability of liposomes made from mitochondrial inner membrane phospholipids–comparison with isolated mitochondria. Journal of Membrane Biology 155, 167174.CrossRefGoogle ScholarPubMed
Brown, GC & Brand, MD (1986) Changes in the permeability to protons and other cations at high proton motive force in rat liver mitochondria. Biochemical Journal 234, 7581.CrossRefGoogle ScholarPubMed
Brown, GC & Brand, MD (1991) On the nature of the mitochondrial proton leak. Biochimica et Biophysica Acta 1059, 5562.CrossRefGoogle ScholarPubMed
Campfield, LA, Smith, FJ & Burn, P (1996) The OB protein (leptin) pathway — a link between adipose tissue mass and central neural networks. Hormone and Metabolic Research 28, 619632.CrossRefGoogle ScholarPubMed
Campfield, LA, Smith, FJ, Guisez, Y, Devos, R & Burn, P (1995) Recombinant mouse ob protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546549.CrossRefGoogle ScholarPubMed
Caro, JF, Sinha, MK, Kolaczynski, JW, Zhang, PL & Considine, RV (1996) Leptin: the tale of an obesity gene. Diabetes 45, 14551462.CrossRefGoogle ScholarPubMed
Collins, S, Kuhn, CM, Petro, AE, Swick, AG, Chrunyk, BA & Surwit, RS (1996) Role of leptin in fat regulation. Nature 380, 677.CrossRefGoogle ScholarPubMed
Digby, JE, Montague, CT, Sewter, CP, Sanders, L, Wilkinson, WO, O'rahilly, S & Prim, JB (1998) Thiazolidinedione exposure increases the expression of uncoupling protein 1 in cultured human adipocytes. Diabetes 47, 138141.CrossRefGoogle Scholar
Enerbäck, S, Jacobsson, A, Simpson, EM, Guerra, C, Yamashits, H, Harper, M-E & Kozak, LP (1997) Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 9094.CrossRefGoogle Scholar
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, 269272.CrossRefGoogle ScholarPubMed
Flier, JS (1997) Leptin expression and action: new experimental paradigms. Proceedings of the National Academy of Sciences USA 94, 42424245.CrossRefGoogle ScholarPubMed
Foster, DO (1986) Quantitative role of brown adipose tissue in thermogenesis. In Brown Adipose Tissue, pp. 3152 [Trayhum, P and Nicholls, DG, editors]. London: Amold.Google Scholar
Foster, DO & Frydman, ML (1979) Tissue distribution of coldinduced thermogenesis in conscious warm- and cold-acclimated rats reevaluated from changes in tissue blood flow. Canadian Journal of Physiology and Pharmacology 57, 257270.CrossRefGoogle ScholarPubMed
Gong, D-W, He, Y, Karas, M & Reitman, M (1997) Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, β3-adrenergic agonists and leptin. Journal of Biological Chemistry 272, 2412924132.CrossRefGoogle ScholarPubMed
Hafner, RP, Nobes, CD, Mcgown, AD & Brand, MD (1988) Altered relationship between proton motive force and respiration rate in non-phosphorylating liver mitochondria isolated from rats of different thyroid hormone status. European Journal of Biochemistry 178, 511518.CrossRefGoogle Scholar
Halaas, JL, Gajiwala, KS, Maffei, M, Cohen, SL, Chait, BT, Rabinowitz, D, Lallone, RL, Burley, SK & Friedman, JM (1995) Weightreducing effects of the plasma protein encoded by the obese gene. Science 269, 543546.CrossRefGoogle ScholarPubMed
Harper, M-E, Ballantyne, JS, Leach, M & Brand, MD (1993) Effects of thyroid hormones on oxidative phosphorylation. Biochemical Society Transactions 21, 785792.CrossRefGoogle ScholarPubMed
Harper M-E, & Brand, MD (1993) The quantitative contribution of mitochondrial proton leak and ATP turnover reactions to the changed respiration rates of hepatocytes from rats of different thyroid status. Journal of Biological Chemistry 268, 1485014860.CrossRefGoogle Scholar
Harper, M-E & Brand, MD (1994) Hyperthyroidism stimulates mitochondrial proton leak and ATP turnover in rat hepatocytes but does not change the overall kinetics of substrate oxidation reactions. Canadian Journal of Physiology and Pharmacology 72, 899908.CrossRefGoogle Scholar
Hwa, JJ, Fawzi, AB, Graziano, MP, Ghibaudi, L, Williams, P, van Heek, M, Davis, H, Rudinski, M, Sybertz, E & Strader, CD (1997) Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice. American Journal of Physiology 272, R1204R1209.Google ScholarPubMed
Kennedy, GC (1953) The role of depot fat in the hypothalamic control of food intake in the rat. Proceedings of the Royal Society 140B, 578592.Google Scholar
Klaus, S, Casteilla, L, Bouillaud, F & Ricquier, D (1991) The uncoupling protein UCP: a membraneous mitochondrial ion carrier in brown adipose tissue. International Journal of Biochemistry 23, 791801.CrossRefGoogle ScholarPubMed
Koyama, K, Chen, G, Lee, Y & Unger, RH (1997) Tissue triglycerides, insulin resistance, and insulin production: implications for hyperinsulinemia of obesity. American Journal of Physiology 273, E708E713.Google ScholarPubMed
Lanni, A, De Felice, M, Lombardi, A, Moreno, M, Fleury, C, Ricquier, D & Goglia, F (1997) Induction of UCP2 mRNA by thyroid hormones in rat heart. FEBS Letters 418, 171174.CrossRefGoogle ScholarPubMed
Larkin, S, Mull, E, Miao, W, Pittner, R, Albrandt, K, Moore, C, Young, A, Denaro, M & Beaumont, K (1997) Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone. Biochemical and Biophysical Research Communications 240, 222227.CrossRefGoogle ScholarPubMed
Larrouy, D, Laharrague, P, Carrera, G, Viguerie-Bascands, N, Levi-meyrueis, C, Fleury, C, Pecqueur, C, Nibbelink, M, André, M, Casteilla, L & Ricquier, D (1997) Kupffer cells are a dominant site of uncoupling protein 2 expression in rat liver. Biochemical and Biophysical Research Communications 235, 760764.CrossRefGoogle ScholarPubMed
Liu, YL, Emilsson, V & Cawthome, MA (1997) Leptin inhibits glycogen synthesis in the isolated soleus muscle of obese (ob/ob) mice. FEBS Letters 411, 351355.CrossRefGoogle ScholarPubMed
Lönnqvist, F & Schalling, M (1997) Role of leptin and its receptor in human obesity. Current Opinion in Endocrinology and Diabetes 4, 164171.CrossRefGoogle Scholar
Masaki, T, Yoshimatsu, H, Kakuma, T, Hidaka, S, Kurokawa, M & Sakata, T (1997) Enhanced expression of uncoupling protein 2 gene in rat white adipose tissue and skeletal muscle following chronic treatment with thyroid hormone. FEBS Letters 418, 323326.CrossRefGoogle ScholarPubMed
Matsuda, J, Hosoda, K, Itoh, H, Son, C, Doi, K, Tanaka, T, Fukunaga, Y, Inoue, G, Nishmura, H, Yoshimasa, Y, Yamori, Y & Nakao, K (1997) Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs: their gene expression in rats fed high-fat diet. FEBS Letters 418, 200204.CrossRefGoogle ScholarPubMed
Melia, HP, Mcbennett, SM, Andrews, JF & Porter, RK (1997) Leptin reverses the increased proton leak observed in liver mitochondria from obese mice to leak rates observed in lean controls. International Journal of Obesity 21, S33.Google Scholar
Millet, L, Vidal, H, Andreelli, F, Larrouy, D, Riou, JP, 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, 26652670.CrossRefGoogle ScholarPubMed
Mitchell, P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic type of mechanism. Nature 191, 144148.CrossRefGoogle ScholarPubMed
Nicholls, DG (1974) The influence of respiration and ATP hydrolysis on the proton-electrochemical gradient across the inner membrane of rat liver mitochondria as determined by ion distribution. European Journal of Biochemistry 50, 305315.CrossRefGoogle ScholarPubMed
Nicholls, DG (1997) The non-ohmic proton leak – 25 years on. Bioscience Reports 17, 251257.CrossRefGoogle Scholar
Nicholls, DG, Bernson, V & Heaton, G (1978) The identification of the component in the inner membrane responsible for regulating energy dissipation. In Effectors of Thermogenesis, pp. 119134 [Girardier, L and Seydoux, J, editors]. Basel: Birkhauser Verlag.Google Scholar
Nicholls, DG & Ferguson, SJ (1992) Bioenergetics 2. London: Academic Press.Google Scholar
Nicholls, DG & Locke, RM (1984) Thermogenic mechanisms in brown fat. Physiological Reviews 64, 164.CrossRefGoogle ScholarPubMed
Nicholls, DG & Rial, E (1974) Measurement of proton leakage across mitochondrial inner membranes and its relation to proton motive force. Methods in Enzymology 174, 8594.CrossRefGoogle Scholar
Pallett, AL, Morton, NM, Cawthorne, MA & Emilsson, V (1997) Leptin inhibits secretion and reduces insulin mRNA levels in rat isolated pancreatic islets. Biochemical and Biophysical Research Communications 238, 267270.CrossRefGoogle ScholarPubMed
Palmieri, F (1994) Mitochondrial carrier proteins. FEBS Letters 346, 4854.CrossRefGoogle ScholarPubMed
Paulik, MA & Lenhard, JM (1997) Thiazolidines inhibit akaline phosphatase while increasing expression of uncoupling protein, deiodinase, and increasing mitochondrial mass in C3H10T/2 cells. Cell and Tissue Research 290, 7987.CrossRefGoogle Scholar
Pelleymounter, MA, Cullen, MJ, Baker, MB, Hecht, R, Winters, D, Boone, T & Collins, F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540543.CrossRefGoogle ScholarPubMed
Porter, RK & Brand, MD (1993) Body mass dependence of H+ leak in mitochondria and its relevance to metabolic rate. Nature 268, 628630.CrossRefGoogle Scholar
Porter, RK & Brand, MD (1995 a) Cellular oxygen consumption depends on body mass. American Journal of Physiology 268, R641R650.Google Scholar
Porter, RK & Brand, MD (1995 b) Causes of differences in respiration rate of hepatocytes from mammals of different body mass. American Journal of Physiology 269, R1213R1224.Google ScholarPubMed
Porter, RK, Hulbert, AJ & Brand, MD (1996) Allometry of mitochondrial proton leak. influence of membrane surface area and fatty acid composition. American Journal of Physiology 271, R1550R1560.Google ScholarPubMed
Porter, RK, Mcbennett, SM, Macdonald, ZI & Andrews, JF (1997) Increased proton leak in liver mitochondria from obese mice compared with lean controls. Proceedings of the Nutrition Society 56, 198A.Google Scholar
Puigserver, P, Vazquez, F, Bonet, ML, Pico, C & Palou, A (1996) In vitro and in vivo induction of brown adipocyte uncoupling protein (thermogenin) by retinoic acid. Biochemical Journal 317, 827833.CrossRefGoogle Scholar
Ricquier, D & Kader, J-C (1978) Mitochondrialg protein alteration in active brown fat: a sodium dodecyl sulfate-polyacrylamide gel electrophoretic study. Biochemical and Biophysical Research Communications 873, 577583.Google Scholar
Rohlfs, EM, Daniel, KW, Premont, RT, Kozak, LP & Collins, S (1995) Regulation of the uncoupling protein gene (UCP) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalised brown adipose cell lines. Journal of Biological Chemistry 270, 1072310732.CrossRefGoogle Scholar
Rolfe, DFS & Brand, MD (1996 a) Proton leak and control of oxidative phosphorylation in perfused, resting rat muscle. Biochimica et Biophysica Acta 1276, 4550.CrossRefGoogle Scholar
Rolfe, DFS & Brand, MD (1996 b) The contribution of mitochondrial proton leak to the rate of respiration in rat skeletal muscle and SMR. American Journal of Physiology 271, C1380C1389.CrossRefGoogle Scholar
Rolfe, DFS & Brand, MD (1997) The physiological significance of mitochondrial proton leak in animal cells and tissues. Bioscience Reports 17, 916.CrossRefGoogle ScholarPubMed
Rolfe, DFS & Brown, GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate. Physiological Reviews 77, 731758.CrossRefGoogle ScholarPubMed
Rolfe, DFS, Hulbert, AJ & Brand, MD (1994) Characteristics of mitochondrial proton leak and control of oxidative phosphorylation in the major oxygen-consuming tissues of the rat. Biochimica et Biophysica Acta 1118, 405416.CrossRefGoogle Scholar
Rothwell, NJ & Stock, MJ (1986)Brown adipose tissue and dietinduced thermogenesis. In Brown Adipose Tissue, pp. 269298 [Trayhum, P and Nicholls, DG, editors]. London: Arnold.Google Scholar
Scarpace, PJ, Matheny, M, Pollock, BH & Tumer, N (1997) Leptin increases uncoupling protein expression and energy metabolism. American Journal of Physiology 273, E226E230.Google Scholar
Shimabukuro, M, Koyama, K, Chen, G, Wang, MY, Trieu, F, Lee, Y, Newgard, CB & Unger, RH (1997 a) Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proceedings of the National Academy of Sciences USA 94, 46374641.CrossRefGoogle ScholarPubMed
Shimabukuro, M, Zhou, YT, Lee, Y & Unger, RH (1997 b) Induction of uncoupling protein-2 mRNA by troglitazone in pancreatic islets of Zucker diabetic fatty rats. Biochemical and Biophysical Research Communications 237, 359361.CrossRefGoogle ScholarPubMed
Silva, JE & Rabelo, R (1997) Regulation of the uncoupling protein gene expression. European Journal of Endocrinology 136, 251264.CrossRefGoogle ScholarPubMed
Solanes, G, Vidal-puig, A, Grucjic, D, Flier, JS & Lowell, BB (1997) The human uncoupling protein-3 gene. Journal of Biological Chemistry 272, 2543325436.CrossRefGoogle ScholarPubMed
Stephens, TW, Basinski, M, Bristow, PK, Bue-valleskey, JM, Burgett, SG, Craft, L, Hale, J, Hoffmann, J, Hsiung, HM, Kriauciunas, A, Mackellar, W, Rosteck, PR Jr, Smith, D, Tinsley, FC, Zhang, X-Y & Heiman, M (1995) The role of neuropeptide Y in the anti-obesity action of the obese gene product. Nature 337, 530532.CrossRefGoogle Scholar
Tartaglia, LA, Demdksi, M, Weng, X, Deng, N, Culpepper, J, Devos, R, Richards, GJ, Campfield, LA, Clark, FT, Deeds, J, Muir, C, Sanker, S, Moriarty, A, Moore, KJ, Smutho, JS, Mays, GG, Woolf, EA, Monroe, CA & Tepper, RI (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 12631271.CrossRefGoogle ScholarPubMed
Trayhum, P (1996) New insights into the development of obesity: obese genes and the leptin system. Proceedings of the Nutrition Society 55, 783791.CrossRefGoogle Scholar
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, 7982.CrossRefGoogle ScholarPubMed
Zhang, Y, Procenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425432.CrossRefGoogle ScholarPubMed
Zhou, Y-T, Shimabukuro, M, Koyama, K, Lee, Y, Wang, M-Y, Trieu, F, Newgard, CB & Unger, RH (1997) Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation. Proceedings of the National Academy of Sciences USA 94, 63866390.CrossRefGoogle ScholarPubMed