Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-26T09:13:00.145Z Has data issue: false hasContentIssue false

Signalling in body-weight homeostasis: neuroendocrine efferent signals

Published online by Cambridge University Press:  28 February 2007

Jonathan Webber*
Affiliation:
School of Medical and Surgical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK
Ian A. Macdonald
Affiliation:
School of Medical and Surgical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK
*
*Corresponding author: Dr Jonathan Webber, fax +44 (0)115 919 4427, email jonathan.webber@nottingham.ac.uk
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.

Whilst a number of neuroendocrine afferent signals are implicated in body-weight homeostasis, the major efferent pathway is the sympathetic nervous system (SNS), which affects both energy expenditure and substrate utilization. Thyroid hormones and their interactions with the SNS may also have a role to play. Some of the variability in resting energy expenditure can be explained by differences in SNS activity, and β-blockade can reduce energy expenditure and diet-induced thermogenesis in Caucasians. Excess energy intake leads to SNS activation and increased diet-induced thermogenesis. A relationship has also been demonstrated between spontaneous physical activity and SNS activity. In many animal models the SNS activates brown adipose tissue thermogenesis, hence increasing diet-induced thermogenesis and dissipating excess energy as heat. This effect is mediated via β3-adrenoceptors and activation of an uncoupling protein unique to brown adipose tissue. Homologous proteins have been identified in human tissues and may play a role in human energy expenditure. How the SNS is implicated in this process is unclear at present. β3-Adrenoceptor polymorphism has been associated both with lower resting energy expenditure in some populations and with reduced autonomic nervous system activity. SNS effects on substrate cycling may also play a role. In the development of obesity the effects of the SNS in promoting lipolysis and fat oxidation are likely to be at least as important as its effects on thermogenesis. β-Blockade has relatively small effects on energy expenditure, but more pronounced effects on reducing lipid oxidation, so tending to favour fat storage and weight gain. Low lipid oxidation is a risk factor for weight gain, and there is some evidence that low basal sympathetic nerve activity in muscle is associated with this process. Overall, the relationship between SNS activity and obesity is complex, with evidence of low SNS activity occurring in some, but not all, studies.

Type
Meeting Report
Copyright
Copyright © The Nutrition Society 2000

References

Acheson, KJ, Ravussin, E, Schoeller, DA, Christin, L, Bourquin, L, Baertschi, P, Danforth, E Jr & Jequier, E (1988) Two week stimulation or blockade of the sympathetic nervous system in man; influence on body weight, body composition and twenty four hour energy expenditure. Metabolism 37, 9198.CrossRefGoogle ScholarPubMed
Acheson, KJ, Ravussin, E, Wahren, J & Jequier, E (1984) Thermic effect of glucose in man: obligatory and facultative thermogenesis. Journal of Clinical Investigation 74, 15721580.CrossRefGoogle ScholarPubMed
Arner, P & Hoffstedt, J (1999) Adrenoceptor genes in human obesity. Journal of Internal Medicine 245, 667672.CrossRefGoogle ScholarPubMed
Astrup, A, Andersen, T, Christensen, NJ, Bulow, J, Madsen, J, Breum, L & Quaade, F (1990) Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans. American Journal of Clinical Nutrition 51, 331337.CrossRefGoogle ScholarPubMed
Astrup, A, Buemann, B, Christensen, NJ, Madsen, J, Gluud, C, Bennett, P & Svenstrup, B (1992) The contribution of body composition, substrates and hormones to the variability in energy expenditure and substrate utilization in premenopausal women. Journal of Clinical Endocrinology and Metabolism 74, 279286.Google Scholar
Astrup, A, Buemann, B, Toubro, S, Ranneries, C & Raben, A (1996) Low resting metabolic rate in subjects predisposed to obesity: a role for thyroid status. American Journal of Clinical Nutrition 63, 879883.CrossRefGoogle ScholarPubMed
Astrup, A, Gotzsche, PC, de Werken, K, Ranneries, C, Toubro, S, Raben, A & Buemann, B (1999) Meta-analysis of resting metabolic rate in formerly obese subjects. American Journal of Clinical Nutrition 69, 11171122.CrossRefGoogle ScholarPubMed
Astrup, A, Simonsen, L, Bulow, J, Madsen, J & Christensen, NJ (1989) Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle. American Journal of Physiology 257, E340-E345.Google ScholarPubMed
Bartness, TJ & Bamshad, M (1998) Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. American Journal of Physiology 275, R1399-R1411.Google ScholarPubMed
Bilezikian, JP & Loeb, JN (1983) The influence of hyperthyroidism and hypothyroidism on a- and b-adrenergic receptor systems and adrenergic responsiveness. Endocrine Reviews 4, 378388.CrossRefGoogle Scholar
Blaak, EE, Saris, WHM & van Baak, MA (1993) Adrenoceptor subtypes mediating catecholamine-induced thermogenesis in man. International Journal of Obesity 17, S78S81.Google ScholarPubMed
Boss, O, Samec, S, Paoloni-Giacobino, A, Rossier, C, Dulloo, A, Seydoux, J, Muzzin, P & Giacobino, JP (1997) Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue specific expression. FEBS Letters 408, 3942.CrossRefGoogle ScholarPubMed
Buemann, B, Astrup, A, Madsen, J & Christensen, NJ (1992) A 24-h energy expenditure study on reduced-obese and nonobese women: effect of b-blockade. American Journal of Clinical Nutrition 56, 662670.CrossRefGoogle Scholar
Bukkens, SGF, McNeill, G, Smith, JS & Morrison, DC (1991) Post-prandial thermogenesis in obese women and weight-matched controls. International Journal of Obesity 15, 147154.Google Scholar
Christin, L, O'Connell, M, Bogardus, C, Danforth, E & Ravussin, E (1993) Norepinephrine turnover and energy expenditure in Pima Indian and white men. Metabolism 42, 723729.CrossRefGoogle ScholarPubMed
Clement, K, Vaisse, C, Manning, B, Basdevant, A, Guy-Grand, B, Ruiz, J, Silver, K, Shuldiner, AR, Froguel, P & Strosberg, AD (1995) Genetic variation in the b3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. New England Journal of Medicine 333, 352354.CrossRefGoogle Scholar
Connacher, AA, Bennet, WM, Jung, RT, Bier, DM, Smith, CCT, Scrimgeour, GM & Rennie, MJ (1991) Effect of adrenaline infusion on fatty acid and glucose turnover in lean and obese human subjects in the post-absorptive and fed states. Clinical Science 81, 635644.CrossRefGoogle ScholarPubMed
Connacher, AA, Jung, RT, Mitchell, PEG, Ford, RP, Leslie, P & Illingworth, P (1988) Heterogeneity of noradrenergic thermic responses in obese and lean humans. International Journal of Obesity 12, 267276.Google ScholarPubMed
Cori, CF & Buchwald, KW (1930) Effect of continuous injection of epinephrine on the carbohydrate metabolism, basal metabolism and vascular system of normal man. American Journal of Physiology 95, 7178.CrossRefGoogle Scholar
Enerback, S, Jacobsson, A, Simpson, EM, Guerra, C, Yamashita, H, Harper, ME & 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-Meyruies, C, Bouillaud, F, Seldin, MF, Surwit, RS, Ricquier, D & Warden, CH (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinaemia. Nature Genetics 15, 269272.CrossRefGoogle Scholar
Fogelholm, M, Valve, R, Kukkonen-Harjula, K, Nenonen, A, Hakkarainen, V, Laakso, M & Uusitupa, M (1998) Additive effects of the mutations in the b3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women. Journal of Clinical Endocrinology and Metabolism 83, 42464250.Google Scholar
Fox, CS, Esparza, J, Nicolson, M, Bennett, PH, Schulz, LO, Valencia, ME & Ravussin, E (1998) Is a low leptin concentration, a low resting metabolic rate, or both the expression of the ‘thrifty phenotype’? Results from Mexican Pima Indians. American Journal of Clinical Nutrition 68, 10531057.CrossRefGoogle ScholarPubMed
Friedman, JM & Halaas, JL (1998) Leptin and the regulation of body weight in mammals. Nature 395, 763770.CrossRefGoogle ScholarPubMed
Gong, D-W, He, Y, Karas, M & Reitman, M (1997) Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, b3-adrenergic agonists and leptin. Journal of Biological Chemistry 272, 2412924132.CrossRefGoogle Scholar
Haynes, WG, Morgan, DA, Walsh, SA, Mark, AL & Sivitz, WI (1997) Receptor-mediated regional sympathetic nerve activation by leptin. Journal of Clinical Investigation 100, 270278.CrossRefGoogle ScholarPubMed
Hill, JO & Wyatt, HR (1999) Relapse in obesity treatment: biology or behaviour? American Journal of Clinical Nutrition 69, 10641065.CrossRefGoogle ScholarPubMed
Himms-Hagen, J (1990) Brown adipose tissue thermogenesis: role in thermoregulation, energy regulation and obesity. In Regulation of Body Weight: Biological and Behavioural Mechanisms, pp. 4860 [Schonbaum, E and Lomax, P, editors]. New York: Pergamon.Google Scholar
Jensen, MD, Haymond, MW, Gerich, JE, Cryer, PE & Miles, JM (1987) Lipolysis during fasting: decreased suppression by insulin and increased stimulation by epinephrine. Journal of Clinical Investigation 79, 207213.CrossRefGoogle ScholarPubMed
Jequier, E (1990) Energy metabolism in obese patients before and after weight loss, and in patients who have relapsed.International Journal of Obesity 14, 5964.Google ScholarPubMed
Johnson, AB, Webber, J, Mansell, P, Gallen, I, Allison, SP & Macdonald, IA (1995) Cardiovascular and metabolic responses to adrenaline infusion in patients with short-term hypothyroidism. Clinical Endocrinology 43, 747751.CrossRefGoogle ScholarPubMed
Kurpad, AV, Kulkarni, RN, Sheela, ML & Shetty, PS (1989) Thermogenic responses to graded doses of noradrenaline in undernourished Indian male subjects. British Journal of Nutrition 61, 201208.CrossRefGoogle ScholarPubMed
Kush, RD, Young, JB, Katzeff, HL, Danforth E, Jr, Garrow, JS, Scheidegger, K, Ravussin, E, Sims, EAH, Horton, ES & Landsberg, L (1986) Effect of diet on energy expenditure and plasma norepinephrine in lean and obese Pima Indians. Metabolism 35, 11101120.CrossRefGoogle ScholarPubMed
Kyle, LH (1950) Clinical applications of the basal metabolism test. Medical Clinics of North America 34, 18391851.CrossRefGoogle Scholar
Landsberg, L (1986) Diet, obesity and hypertension: An hypothesis involving insulin, the sympathetic nervous system and adaptive thermogenesis. Quarterly Journal of Medicine 61, 10811090.Google ScholarPubMed
Landsberg, L & Young, JB (1978) Fasting, feeding and regulation of the sympathetic nervous system. New England Journal of Medicine 298, 12951301.CrossRefGoogle ScholarPubMed
Large, V, Hellstrom, L, Reynisdottir, S, Lonnqvist, F, Eriksson, P, Lannfelt, L & Arner, P (1997) Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associated with altered adipocyte beta-2 adrenoceptor function. Journal of Clinical Investigation 100, 30053013.CrossRefGoogle ScholarPubMed
Levine, JA, Eberhardt, NL & Jensen, MD (1999) Role of non-exercise activity thermogenesis in resistance to fat gain in humans. Science 283, 212214.CrossRefGoogle Scholar
Li, H, Matheny, M & Scarpace, PJ (1997) b3-Adrenergic-mediated suppression of leptin gene expression in rats. American Journal of Physiology 272, E1031-E1036.Google ScholarPubMed
Macdonald, IA (1995) Advances in our understanding of the role of the sympathetic nervous system in obesity. International Journal of Obesity 19, S2S7.Google ScholarPubMed
Meirhaeghe, A, Helbecque, N, Cottel, D & Amouyel, P (1999) b2-Adrenoceptor gene polymorphism, body weight, and physical activity. Lancet 353, 896.CrossRefGoogle Scholar
Muntzel, MS, Morgan, DA, Mark, AL & Johnson, AK (1994) Intracerebroventricular insulin produces non-uniform regional increases in sympathetic nerve activity.American Journal of Physiology 267, R1350-R1355.Google Scholar
Nacht, CA, Christin, L, Temler, E, Chiolero, R, Jequier, E & Acheson, KJ (1987) Thermic effect of food: possible implication of parasympathetic nervous system. American Journal of Physiology 258, E481E488.Google Scholar
Newsholme, EA (1980) A possible metabolic basis for the control of body weight. New England Journal of Medicine 302, 400405.CrossRefGoogle ScholarPubMed
O'Dea, K, Esler, M, Leonard, P, Stockigt, JR & Nestel, P (1982) Noradrenaline turnover during under- and over-eating in normal weight subjects. Metabolism 31, 896899.CrossRefGoogle ScholarPubMed
Peterson, HR, Rothschild, M, Weinberg, CR, Fell, RD, McLeish, KR & Pfeifer, MA (1988) Body fat and the activity of the autonomic nervous-system. New England Journal of Medicine 318, 10771083.CrossRefGoogle ScholarPubMed
Prentice, AM & Jebb, SA (1995) Obesity in Britain: Glutony or sloth? British Medical Journal 311, 437439.CrossRefGoogle ScholarPubMed
Raben, A, Macdonald, IA & Astrup, A (1997) Replacement of dietary fat by sucrose or starch: Effects on 14 days' ad libitum energy intake, energy expenditure and body weight in formerly obese and non-obese subjects. International Journal of Obesity 21, 846859.CrossRefGoogle ScholarPubMed
Reaven, GM, Lithell, H & Landsberg, L (1996) Hypertension and associated metabolic abnormalities-the role of insulin resistance and the sympathoadrenal system. New England Journal of Medicine 334, 374381.CrossRefGoogle ScholarPubMed
Rossner, S, Taylor, CL, Byington, RP & Furberg, CD (1990) Long term propranolol treatment and changes in body weight after myocardial infarction. British Medical Journal 300, 902903.CrossRefGoogle ScholarPubMed
Saad, MF, Alger, SA, Zurlo, F, Young, JB, Bogardus, C & Ravussin, E (1991) Ethnic differences in sympathetic nervous system-mediated energy expenditure. American Journal of Physiology 261, E789-E794.Google ScholarPubMed
Sakane, N, Yoshida, T, Umekawa, T, Kpgure, A & Kondo, M (1999) b2-Adrenoceptor gene polymorphism and obesity. Lancet 353, 1976.CrossRefGoogle Scholar
Scherrer, U, Randin, D, Tappy, L, Vollenweider, P, Jequier, E & Nicod, P (1994) Body fat and sympathetic nerve activity in healthy subjects. Circulation 89, 26342640.CrossRefGoogle ScholarPubMed
Schneeberger, D, Tappy, L, Temler, E & Jequier, E (1991) Effects of muscarinic blockade on insulin secretion and on glucose-induced thermogenesis in lean and obese human subjects. European Journal of Clinical Investigation 21, 608615.CrossRefGoogle ScholarPubMed
Schrauwen, P, Xia, J, Bogardus, C, Pratley, RE & Ravussin, E (1999) Skeletal muscle uncoupling protein-3 expression is a determinant of energy expenditure in Pima Indians. Diabetes 48, 146149.CrossRefGoogle ScholarPubMed
Schwartz, RS, Jaeger, LF, Silberstein, S & Veith, RC (1987) Sympathetic nervous system activity and the thermic effect of feeding in man. International Journal of Obesity 11, 141149.Google ScholarPubMed
Schwartz, RS, Jaeger, LF & Veith, RC (1988) Effect of clonidine on the thermic effect of feeding in humans. American Journal of Physiology 254, R90-R94.Google ScholarPubMed
Schwartz, RS, Jaeger, LF & Veith, RC (1990a) The thermic effect of feeding in older men: The importance of the sympathetic nervous system. Metabolism 39, 733737.CrossRefGoogle ScholarPubMed
Schwartz, RS, Jaeger, LF, Veith, RC & Lakshminarayan, S (1990b) The effect of diet or exercise on plasma norepinephrine kinetics in moderately obese young men. International Journal of Obesity 14, 111.Google ScholarPubMed
Shihara, N, Yasuda, K, Moritani, T, Ue, H, Adachi, T, Tanaka, H, Tsuda, K & Seino, Y (1999) The association between TrpArg polymorphism of the b3-adrenergic receptor and autonomic nervous system activity. Journal of Clinical Endocrinology and Metabolism 84, 16231627.Google Scholar
Snitker, S, Tataranni, PA & Ravussin, E (1998) Respiratory quotient is inversely associated with muscle sympathetic nerve activity. Journal of Clinical Endocrinology and Metabolism 83, 39773979.CrossRefGoogle ScholarPubMed
Spraul, M, Anderson, EA, Bogardus, C & Ravussin, E (1994) Muscle sympathetic nerve activity in response to glucose ingestion. Impact of plasma insulin and body fat. Diabetes 43, 191196.CrossRefGoogle ScholarPubMed
Spraul, M, Ravussin, E, Fontvieille, AM, Rising, R, Larson, DE & Anderson, EA (1993) Reduced sympathetic activity. A potential mechanism predisposing to body weight gain. Journal of Clinical Investigation 92, 17301735.CrossRefGoogle ScholarPubMed
Thomas, SA & Palmiter, RD (1997) Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387, 9497.CrossRefGoogle ScholarPubMed
Toubro, S, Sorensen, IA, Bonn, B, Christensen, NJ & Astrup, A (1996) Twenty-four hour energy expenditure: the role of body composition, thyroid status, sympathetic activity and family membership. Journal of Clinical Endocrinology and Metabolism 81, 26702674.Google ScholarPubMed
Trayhurn, P, Duncan, JS & Rayner, DV (1995) Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system. Biochemical Journal 311, 729733.CrossRefGoogle Scholar
Tremblay, A (1992) Human obesity: a defect in lipid oxidation or in thermogenesis? International Journal of Obesity 16, 953957.Google ScholarPubMed
Tremblay, A, Coveney, JP, Despres, JP, Nadeau, A & Prud'homme, D (1992) Increased resting metabolic rate and lipid oxidation in exercise-trained individuals: evidence for a role of beta adrenergic stimulation. Canadian Journal of Physiology and Pharmacology 70, 13421347.CrossRefGoogle ScholarPubMed
Troisi, RJ, Weiss, ST, Parker, DR, Sparrow, D, Young, JB & Landsberg, L (1991) Relationship of obesity and diet to sympathetic nervous system activity. Hypertension 17, 669677.CrossRefGoogle Scholar
Vernet, O, Nacht, C-A, Christin, L, Schutz, Y, Danforth E, Jr & Jequier, E (1987) b-adrenergic blockade and intravenous nutrient-induced thermogenesis in lean and obese women. American Journal of Physiology 253, E65-E71.Google Scholar
Walston, J, Silver, K, Bogardus, C, Knowler, WC, Celi, FS, Austin, S, Manning, B, Strosberg, AD, Stern, MP, Raben, N, Sorkin, JD, Roth, J & Shuldiner, AR (1995) Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the b3-adrenergic-receptor gene. New England Journal of Medicine 333, 343347.CrossRefGoogle ScholarPubMed
Webber, J, Donaldson, M, Allison, SP, Fukagawa, NK & Macdonald, IA (1994a) The effects of weight loss in obese subjects on the thermogenic, metabolic and haemodynamic responses to the glucose clamp. International Journal of Obesity 18, 725730.Google Scholar
Webber, J, Taylor, J, Greathead, H, Dawson, J, Buttery, PJ & Macdonald, IA (1994b) A comparison of the thermogenic, metabolic and haemodynamic responses to infused adrenaline in lean and obese subjects. International Journal of Obesity 18, 717724.Google ScholarPubMed
Webber, J, Taylor, J, Greathead, H, Dawson, J, Buttery, PJ & Macdonald, IA (1995) The effects of fasting on the thermogenic, metabolic and cardiovascular responses to infused epinephrine. British Journal of Nutrition 74, 477490.CrossRefGoogle Scholar
Weigle, DS, Selfridge, LE, Schwartz, MW, Seeley, RJ, Cummings, DE, Havel, PJ, Kuijper, JL & BeltrandelRio, H (1998) Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fasting. Diabetes 47, 298302.CrossRefGoogle ScholarPubMed
Welle, SL & Campbell, RG (1983) Stimulation of thermogenesis by carbohydrate overfeeding: evidence against sympathetic nervous system mediation. Journal of Clinical Investigation 71, 916925.CrossRefGoogle ScholarPubMed
Welle, SL, Nair, KS & Campbell, RG (1989) Failure of chronic b-adrenergic blockade to inhibit overfeeding-induced thermogenesis in humans. American Journal of Physiology 256, R653-R658.Google Scholar
Welle, S, Schwartz, RG & Statt, M (1991) Reduced metabolic rate during b-adrenergic blockade in humans. Metabolism 40, 619622.CrossRefGoogle Scholar
Widen, E, Lehto, M, Kanninen, T, Walston, J, Shuldiner, AR & Groop, LC (1995) Association of a polymorphism in the b3-adrenergic receptor gene with features of the insulin resistance syndrome in Finns. New England Journal of Medicine 333, 348351.CrossRefGoogle Scholar
Wolfe, RR, Herndon, DN, Jahoor, F, Miyoshi, H & Wolfe, M (1987) Effect of severe burn injury on substrate cycling by glucose and fatty acids. New England Journal of Medicine 317, 403408.CrossRefGoogle ScholarPubMed
Young, JB & Macdonald, IA (1992) Sympathoadrenal activity in human obesity: heterogeneity of findings since 1980. International Journal of Obesity 16, 959967.Google ScholarPubMed
Young, JB & Morrison, SF (1998) Effects of fetal and neonatal environment on sympathetic nervous system development. Diabetes Care 21, S156S160.Google ScholarPubMed
Zurlo, F, Lillioja, S, Puente, AE-D, Nyomba, BL, Raz, I, Saad, MF, Swinburn, BA, Knowler, WC, Bogardus, C & Ravussin, E (1990) Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. American Journal of Physiology 259, E650-E657.Google ScholarPubMed