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The biology of obesity

Published online by Cambridge University Press:  07 March 2007

Paul Trayhurn
Paul Trayhurn
Affiliation:
Neuroendocrine & Obesity Biology Unit, Liverpool Centre for Nutritional Genomics, School of Clinical Sciences, University of Liverpool, University Clinical Departments, Duncan Building, Liverpool L69 3GA, UK
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Abstract

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Obesity is a multidisciplinary area, the ‘biology’ of which encompasses: (1) the fundamental mechanisms of energy balance and its regulation; (2) the biological basis for the development of obesity; (3) adipose tissue function; (4) the biological description of the obese state; (5) the pathological consequences of obesity; (6) the physiological basis for treatment strategies. At a mechanistic level, important developments in recent years include the identification of novel neuroendocrine factors in the control of appetite (such as cocaine- and amphetamine-regulated transcript, the orexins, the endocannabinoids) and the discovery of new peripheral signals (such as leptin, ghrelin). Despite the identification of additional uncoupling proteins (UCP2, UCP3), mitochondrial uncoupling in brown adipose tissue through UCP1 remains the only major mechanism for adaptive thermogenesis. White adipose tissue (WAT) has now moved centre stage in energy balance and obesity research, and there are three main reasons: (1) it is the organ which defines obesity; (2) it is the source of a critical endocrine signal in the control of body weight; (3) it secretes a range of diverse protein factors, termed adipokines, some of which are directly implicated in the pathologies associated with obesity. WAT is now recognised as a key endocrine organ, communicating both with the brain and peripheral tissues through the adipokines. Obesity is characterised by mild inflammation, and WAT may be the main locus of the inflammatory state, producing cytokines, chemokines, acute-phase proteins and angiogenic factors. It has been suggested that inflammation in obesity is principally an adaptive response to hypoxia in clusters of adipocytes within the expanding adipose mass.

Keywords

AdipokinesAppetiteEnergy balanceInflammationObesityWhite adipose tissue
Type
Planary Lecture
Information
Proceedings of the Nutrition Society , Volume 64 , Issue 1 , February 2005 , pp. 31 - 38
Copyright
Copyright © The Nutrition Society 2005

References

Alessi, MC, Bastelica, D, Morange, P, Berthet, B, Leduc, I, Verdier, M, Geel, O & Juhan-Vague, I (2000) Plasminogen activator inhibitor 1, transforming growth factor- β(1), and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 49, 1374–1380.CrossRefGoogle ScholarPubMed
Arch, J (2000) Orexins, feeding and the big picture. British Journal of Nutrition 84, 401–403.Google Scholar
Arita, Y, Kihara, S, Ouchi, N, Takahashi, M, Maeda, K, Miyagawa, J et al. (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochemical and Biophysical Research Communications 257, 79–83.Google Scholar
Ashrafi, K, Chang, FY, Watts, JL, Fraser, AG, Kamath, RS, Ahringer, J & Ruvkun, G (2003) Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421, 268–272.CrossRefGoogle ScholarPubMed
Bandini, LG, Schoeller, DA & Dietz, WH (1990) Energy expenditure in obese and nonobese adolescents. Pediatric Research 27, 198–203.Google Scholar
Bastard, JP, Jardel, C, Bruckert, E, Blondy, P, Capeau, J, Laville, M, Vidal, H & Hainque, B (2000) Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. Journal of Clinical Endocrinology and Metabolism 85, 3338–3342.Google Scholar
Batterham, RL & Bloom, SR (2003) The gut hormone peptide YY regulates appetite. Annals of the New York Academy of Sciences 994, 162–168.CrossRefGoogle ScholarPubMed
Batterham, RL, Cowley, MA, Small, CJ, Herzog, H, Cohen, MA, Dakin, CL, Wren, AM, Brynes, AE, Low, MJ, Ghatei, MA, Cone, RD & Bloom, SR (2002) Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418, 650–654.CrossRefGoogle ScholarPubMed
Berry, EM & Mechoulam, R (2002) Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacology and Therapeutics 95, 185–190.Google Scholar
Bing, C, Bao, Y, Jenkins, J, Sanders, P, Manieri, M, Cinti, S, Tisdale, MJ & Trayhurn, P (2004) Zinc-α2-glycoprotein, a lipid mobilising factor, is expressed in adipocytes and upregulated in mice with cancer cachexia. Proceedings of the National Academy of Sciences USA 101, 2500–2505.Google Scholar
Búllo, M, Garcia-Lorda, P, Megias, I & Salas-Salvado, J (2003) Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obesity Research 11, 525–531.Google Scholar
Cannon, B & Nedergaard, J (2004) Brown adipose tissue: function and physiological significance. Physiological Reviews 84, 277–359.Google Scholar
Chiellini, C, Santini, F, Marsili, A, Berti, P, Bertacca, A, Pelosini, C et al. (2004) Serum haptoglobin: A novel marker of adiposity in humans. Journal of Clinical Endocrinology and Metabolism 89, 2678–2683.Google Scholar
Considine, RV, Sinha, MK, Heiman, ML, Kriauciunas, A, Stephens, TW, Nyce, MR, Ohannesian, JP, Marco, CC, McKee, LJ, Bauer, TL, Caro, JF (1996) Serum immunoreactive leptin concentrations in normal-weight and obese humans. New England Journal of Medicine 334, 292–295.Google Scholar
Cook, KS, Min, HY, Johnson, D, Chaplinsky, RJ, Flier, JS, Hunt, CR & Spiegelman, BM (1987) Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science 237, 402–405.Google Scholar
Das, UN (2001) Is obesity an inflammatory condition? Nutrition 17, 953–966.Google Scholar
Dietze, D, Koenen, M, Rohrig, K, Horikoshi, H, Hauner, H, Eckel, J (2002) Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Diabetes 51, 2369–2376.Google Scholar
Diez-Itza, I, Sanchez, LM, Allende, MT, Vizoso, F, Ruibal, A & Lopez-Otin, C (1993) Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters. European Journal of Cancer 29, 1256–1260.Google Scholar
Di Marzo, V, Goparaju, SK, Wang, L, Liu, J, Batkai, S, Jarai, Z, Fezza, F, Miura, GI, Palmiter, RD, Sugiura, T & Kunos, G (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410, 822–825.Google Scholar
Dulloo, AG & Samec, S (2001) Uncoupling proteins: their roles in adaptive thermogenesis and substrate metabolism reconsidered. British Journal of Nutrition 86, 123–139.Google Scholar
Ehrhart-Bornstein, M, Lamounier-Zepter, V, Schraven, A, Langenbach, J, Willenberg, HS, Barthel, A, Hauner, H, McCann, SM, Scherbaum, WA & Bornstein, SR (2003) Human adipocytes secrete mineralocorticoid-releasing factors. Proceedings of the National Academy of Sciences USA 100, 14211–14216.Google Scholar
Engström, G, Hedblad, B, Stavenow, L, Lind, P, Janzon, L & Lindgarde, F (2003) Inflammation-sensitive plasma proteins are associated with future weight gain. Diabetes 52, 2097–2101.Google Scholar
Festa, A, D'Agostino, R Jr, Williams, K, Karter, AJ, Mayer-Davis, EJ, Tracy, RP & Haffner, SM (2001) The relation of body fat mass and distribution to markers of chronic inflammation. International Journal of Obesity 25, 1407–1415.Google Scholar
Frühbeck, G, Gómez-Ambrosi, J, Muruzabal, FJ, Burrell, MA (2001) The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. American Journal of Physiology 280, E827–E847.Google Scholar
Hale, LP, Price, DT, Sanchez, LM, Demark-Wahnefried, W & Madden, JF (2001) Zinc alpha-2-glycoprotein is expressed by malignant prostatic epithelium and may serve as a potential serum marker for prostate cancer. Clinical Cancer Research 7, 846–853.Google ScholarPubMed
Harris, RB (2000) Leptin – much more than a satiety signal. Annual Review of Nutrition 20, 45–75.Google Scholar
Harrold, JA & Williams, G (2003) The cannabinoid system: a role in both the homeostatic and hedonic control of eating? British Journal of Nutrition 90, 729–734.Google Scholar
Himms-Hagen, J (1989) Brown adipose tissue thermogenesis and obesity. Progress in Lipid Research 28, 67–115.Google Scholar
Hirai, K, Hussey, HJ, Barber, MD, Price, SA & Tisdale, MJ (1998) Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Research 58, 2359–2365.Google Scholar
Höpfl, G, Ogunshola, O & Gassmann, M (2004) HIFs and tumors – causes and consequences. American Journal of Physiology 286, R608–R623.Google Scholar
Hotamisligil, GS (2003) Inflammatory pathways and insulin action. International Journal of Obesity 27, S53–S55 Suppl. 3.Google Scholar
Hotamisligil, GS, Shargill, NS & Spiegelman, BM (1993) Adipose expression of tumor necrosis factor-alpha – direct role in obesity-linked insulin resistance. Science 259, 87–91.Google Scholar
Hotta, K, Funahashi, T, Arita, Y, Takahashi, M, Matsuda, M, Okamoto, Y et al. (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arteriosclerosis, Thrombosis and Vascular Biology 20, 1595–1599.Google Scholar
House of Commons Health Committee (2004) Obesity – Third Report of Session 2003–04 London: The Stationery Office.Google Scholar
Huszar, D, Lynch, CA, Fairchild-Huntress, V, Dunmore, JH, Fang, Q, Berkemeier, LR et al. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141.Google Scholar
Kojima, M, Hosoda, H, Date, Y, Nakazato, M, Matsuo, H & Kangawa, K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–660.Google Scholar
Kojima, M & Kangawa, K (2002) Ghrelin, an orexigenic signaling molecule from the gastrointestinal tract. Current Opinion in Pharmacology 2, 665–668.CrossRefGoogle ScholarPubMed
Kristensen, P, Judge, ME, Thim, L, Ribel, U, Christjansen, KN, Wulff, BS, Clausen, JT, Jensen, PB, Madsen, OD, Vrang, N, Larsen, PJ & Hastrup, S (1998) Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393, 72–76.Google Scholar
Levi-Montalcini, R, Skaper, SD, Dal Toso, R, Petrelli, L & Leon, A (1996) Nerve growth factor: from neurotrophin to neurokine. Trends in Neuroscience 19, 514–520.Google Scholar
Lowell, BB, S-Susulic, V, Hamann, A, Lawitts, JA, Himms-Hagen, J, Boyer, BB, Kozak, LP & Flier, JS (1993) Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740–742.Google Scholar
Masuzaki, H, Paterson, J, Shinyama, H, Morton, NM, Mullins, JJ, Seckl, JR & Flier, JS (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294, 2166–2170.Google Scholar
Meister, B (2000) Control of food intake via leptin receptors in the hypothalamus. Vitamins and Hormones 59, 265–304.Google Scholar
Mercer, JG, Hoggard, N, Williams, LM, Lawrence, CB, Hannah, LT & Trayhurn, P (1996) Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Letters 387, 113–116.Google Scholar
Mohamed-Ali, V, Goodrick, S, Rawesh, A, Katz, DR, Miles, JM, Yudkin, JS, Klein, S & Coppack, SW (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. Journal of Clinical Endocrinology and Metabolism 82, 4196–4200.Google Scholar
Nakazato, M, Murakami, N, Date, Y, Kojima, M, Matsuo, H, Kangawa, K & Matsukura, S (2001) A role for ghrelin in the central regulation of feeding. Nature 409, 194–198.Google Scholar
Ostlund, RE, Yang, JW, Klein, S & Gingerich, R (1996) Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. Journal of Clinical Endocrinology and Metabolism 81, 3909–3913.Google Scholar
Pedersen, BK, Steensberg, A, Fischer, C, Keller, C, Keller, P, Plomgaard, P, Wolsk-Petersen, E & Febbraio, M (2004) The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proceedings of the Nutrition Society 63, 263–267.Google Scholar
Pedersen, BK, Steensberg, A & Schjerling, P (2001) Muscle-derived interleukin-6: possible biological effects Journal of Physiology, London 536, 329–337.CrossRefGoogle Scholar
Peeraully, MR, Jenkins, JR & Trayhurn, P (2004) NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines. American Journal of Physiology 287, E331–E339.Google Scholar
Prentice, AM, Black, AE, Coward, WA & Cole, TJ (1996) Energy expenditure in overweight and obese adults in affluent societies: an analysis of 319 doubly-labelled water measurements. European Journal of Clinical Nutrition 50, 93–97.Google Scholar
Prentice, AM, Black, AE, Coward, WA, Davies, HL, Goldberg, GR, Murgatroyd, PR, Ashford, J, Sawyer, M & Whitehead, RG (1986) High levels of energy expenditure in obese women. British Medical Journal 292, 983–987.Google Scholar
Rajala, MW & Scherer, PE (2003) Minireview: The adipocyte – at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144, 3765–3773.CrossRefGoogle ScholarPubMed
Rayner, DV & Trayhurn, P (2001) Regulation of leptin production: sympathetic nervous system interactions. Journal of Molecular Medicine 79, 8–20.Google Scholar
Ricquier, D & Bouillaud, F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Bio-chemical Journal 345, 161–179.Google Scholar
Rodgers, RJ, Ishii, Y, Halford, JC & Blundell, JE (2002) Orexins and appetite regulation. Neuropeptides 36, 303–325.Google Scholar
Rothwell, NJ & Stock, MJ (1979) A role for brown adipose tissue in diet-induced thermogenesis. Nature 281, 31–35.Google Scholar
Rothwell, NJ, Stock, MJ (1981) Regulation of energy balance. Annual Review of Nutrition 1, 235–256.Google Scholar
Rothwell, NJ, Stock, MJ & Stribling, D (1982) Diet-induced thermogenesis. Pharmacology and Therapeutics l7, 25l – 268.Google Scholar
Rousset, S, Alves-Guerra, MC, Mozo, J, Miroux, B, Cassard-Doulcier, AM, Bouillaud, F & Ricquier, D (2004) The biology of mitochondrial uncoupling proteins. Diabetes 53, S130–S135 Suppl. 1.CrossRefGoogle ScholarPubMed
Russell, ST, Hirai, K & Tisdale, MJ (2002) Role of beta3-adrenergic receptors in the action of a tumour lipid mobilizing factor. British Journal of Cancer 86, 424–428.Google Scholar
Sakurai, T, Amemiya, A, Ishii, M, Matsuzaki, I, Chemelli, RM, Tanaka, H et al. g(1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573–585.Google Scholar
Sanchez, LM, Chirino, AJ & Bjorkman, P (1999) Crystal structure of human ZAG, a fat-depleting factor related to MHC molecules. Science 283, 1914–1919.CrossRefGoogle Scholar
Sartipy, P & Loskutoff, DJ (2003) Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proceedings of the National Academy of Sciences USA 100, 7265–7270.Google Scholar
Schwartz, MW, Seeley, RJ, Campfield, LA, Burn, P & Baskin, DG (1996) Identification of targets of leptin action in rat hypo-thalamus. Journal of Clinical Investigation 98, 1101–1106.Google Scholar
Semenza, GL (2001) HIF-1 and mechanisms of hypoxia sensing. Current Opinion in Cell Biology 13, 167–171.Google Scholar
Stock, MJ (1999) Gluttony and thermogenesis revisited. International Journal of Obesity 23, 1105–1117.Google Scholar
Thim, L, Kristensen, P, Larsen, PJ & Wulff, BS (1998) CART, a new anorectic peptide. International Journal of Biochemistry and Cell Biology 30, 1281–1284.Google Scholar
Thurlby, PL & Trayhurn, P (1979) The role of thermoregulatory thermogenesis in the development of obesity in genetically obese ( ob/ob ) mice pair-fed with lean siblings. British Journal of Nutrition 42, 377–385.Google Scholar
Todorov, PT, McDevitt, TM, Meyer, DJ, Ueyama, H, Ohkubo, I & Tisdale, MJ (1998) Purification and characterization of a tumor lipid-mobilizing factor. Cancer Research 58, 2353–2358.Google Scholar
Trayhurn, P (1984) The development of obesity in animals: the role of genetic susceptibility. Clinical Endocrinology and Metabolism 13, 451–474.Google Scholar
Trayhurn, P & Beattie, JH (2001) Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proceedings of the Nutrition Society 60, 329–339.Google Scholar
Trayhurn, P, Hoggard, N, Mercer, JG & Rayner, DV (1999) Leptin: fundamental aspects. International Journal of Obesity 23, 22–28.Google Scholar
Trayhurn, P, Jones, PM, McGuckin, MM & Goodbody, AE (1982) Effects of overfeeding on energy balance and brown fat thermogenesis in obese ( ob/ob ) mice. Nature 295, 323–325.Google Scholar
Trayhurn, P & Wood, IS (2004) Adipokines: Inflammation and the pleiotropic role of white adipose tissue. British Journal of Nutrition 92, 347–355.Google Scholar
Vega, JA, Garcia-Suarez, O, Hannestad, J, Perez-Perez, M & Germana, A (2003) Neurotrophins and the immune system. Journal of Anatomy 203, 1–19.Google Scholar
Wang, G, Lee, HM, Englander, E & Greeley, GH Jr (2002) Ghrelin – not just another stomach hormone. Regulatory Peptides 105, 75–81.Google Scholar
Weisberg, SP, McCann, D, Desai, M, Rosenbaum, M, Leibel, RL & Ferrante, AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation 112, 1796–1808.Google Scholar
Wenger, RH (2002) Cellular adaptation to hypoxia: O 2 -sensing protein hydroxylases, hypoxia-inducible transcription factors, and O 2 -regulated gene expression. FASEB Journal 16, 1151–1162.CrossRefGoogle Scholar
Wilding, JP (2002) Neuropeptides and appetite control. Diabetic Medicine 19, 619–627.Google Scholar
Wood, IS, Hunter, L & Trayhurn, P (2003) Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues. Biochemical and Biophysical Research Communications 308, 43–49.Google Scholar
Wood, IS & Trayhurn, P (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. British Journal of Nutrition 89, 3–9.Google Scholar
Xu, H, Barnes, GT, Yang, Q, Tan, G, Yang, D, Chou, CJ, Sole, J, Nichols, A, Ross, JS, Tartaglia, LA & Chen, H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation 112, 1821–1830.Google Scholar
Yokota, T, Oritani, K, Takahashi, I, Ishikawa, J, Matsuyama, A, Ouchi, N, Kihara, S, Funahashi, T, Tenner, AJ, Tomiyama, Y & Matsuzawa, Y (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96, 1723–1732.Google Scholar
Yudkin, JS (2003) Adipose tissue, insulin action and vascular disease: inflammatory signals. International Journal of Obesity 27, S25–S28 Suppl. 3.Google Scholar
Yudkin, JS, Stehouwer, CD, Emeis, JJ & Coppack, SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arteriosclerosis, Thrombosis and Vascular Biology 19, 972–978.Google Scholar
Zhang, YY, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homolog. Nature 372, 425–432.Google Scholar
Zhu, Y, Yamanaka, A, Kunii, K, Tsujino, N, Goto, K & Sakurai, T (2002) Orexin-mediated feeding behavior involves both leptin-sensitive and -insensitive pathways. Physiology and Behavior 77, 251–257.Google Scholar