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Methodological approaches to assess body-weight regulation and aetiology of obesity

Published online by Cambridge University Press:  28 February 2007

Amelia Marti ,
Carlos De Miguel ,
Susan A Jebb ,
Max Lafontan ,
Martine Laville ,
Andreu Palou ,
Xavier Remesar ,
Paul Trayhurn  and
J. Alfredo Martinez
Amelia Marti*
Affiliation:
Department of Physiology and Nutrition, University of Navarra, 31008 Pamplona, Spain
Carlos De Miguel
Affiliation:
Department of Biochemistry and Molecular Biology, University of Navarra, 31008 Pamplona, Spain
Susan A Jebb
Affiliation:
MRC Human Nutrition Research, Downhams Lane, Cambridge CB4 1XJ, UK
Max Lafontan
Affiliation:
Unité INSERM 317, Institut Louis Bugnard, Université Paul Sabatier, CHU Rangueil, 31403 Toulouse cedex 4, France
Martine Laville
Affiliation:
Human Nutrition Research Centre of Lyon, INSERM U 449, Lyon, France
Andreu Palou
Affiliation:
Bioquímica i Biologia Molecular, Department de Biologia Molecular, Departament de Biologia Fonamental i Ciències de la Salut, Universitat de les IllesBalears, 07071-Palma de Mallorca, Spain
Xavier Remesar
Affiliation:
Department of Biochemistry and Molecular Biology, Faculty of Biology, >University of Barcelona, Barcelona, Spain
Paul Trayhurn
Affiliation:
Molecular Physiology Group, Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK
J. Alfredo Martinez
Affiliation:
Department of Physiology and Nutrition, University of Navarra, 31008 Pamplona, Spain
*
*Corresponding author: Dr Amelia Marti, fax +34 948 425649, email amarti@unav.es
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Abstract

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Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunities of the molecular era as well as novel whole-body approaches, which will impact on the development of new targets for obesity management and prevention.

Keywords

Obesity genesAdipose tissueEnergy expenditureBody composition
Type
4th Plenary Session (Debate) on ‘Methodological approaches in body-weight regulation’
Information
Proceedings of the Nutrition Society , Volume 59 , Issue 3 , August 2000 , pp. 405 - 411
Copyright
Copyright © The Nutrition Society 2000

References

Andreelli, F, Laville, M, Ducluzeau, PH, Vega, N, Vallier, P, Khalfallah, Y, Riou, JP & Vidal, H (1999) Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients. Diabetologia 42, 358–364.CrossRefGoogle ScholarPubMed
Auboeuf, D, Rieusset, J, Fajas, L, Vallier, P, Frering, V, Riou, JP, Staels, B, Auwerx, J, Laville, M & Vidal, H (1997) Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes 48, 1319–1327.Google Scholar
Beaudet, AL (1998) Genetics and disease. In The Principles of Internal Medicine, pp. 365–395 [Fauci, AS, Braunwald, E, Isselbachaer, KJ, Wilson, JD, Martin, JB, Hauser, SL and Longo, DL, editors]. New York: McGraw-Hill.Google Scholar
Bonet, ML, Puigserver, P, Serra, F, Ribot, J, Vazquez, F, Pico, C & Palou, A (1997) Retinoic acid modulates retinoid X receptor alpha and retinoic acid receptor alpha levels of cultured brown adipocytes. FEBS Letters 406, 196–200.CrossRefGoogle ScholarPubMed
Bray, GA (1999) Afferent signals regulating food intake. Journal of Physiology and Biochemistry 55, 105.Google Scholar
Clarke, SD & Sooja, KK (1998) Molecular methodologies in nutrition research. Journal of Nutrition 128, 2036–2037.CrossRefGoogle ScholarPubMed
Clément, K, Vaisse, C, Lahlou, N, Cabrol, S, Pelloux, V, Cassuto, D, Gourmelen, M, Dina, C, Chambaz, J, Lacorte, JM, Basdevant, A, Bougneres, P, Lebouc, Y, Froguel, P & Guy-Grand, B (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392, 398–401.CrossRefGoogle ScholarPubMed
Closa, D, Alemany, M & Remesar, X (1992) Effect of cold exposure on organ temperatures in Wistar and Zucker fa/fa rat. Journal of Thermic Biology 17, 83–88.Google Scholar
Diaz, EO & Marques-Lopes, I (1999) Measurement of energy expenditure. Journal of Physiology and Biochemistry 55, 102.Google Scholar
Docherty, K (1996) Transgenic animals. Proceedings of the Nutrition Society 55, 613–618.CrossRefGoogle ScholarPubMed
Esteve, M, Rafecas, I, Remesar, X & Alemany, M (1992) Nitrogen balance of lean and obese Zucker rats subjected to a cafeteria diet. International Journal of Obesity 16, 237–244.Google Scholar
Frayn, KN, Coppack, SW & Humphreys, SM (1993) Subcutaneous adipose tissue metabolism studied by local catheterization. International Journal of Obesity 17, Suppl. 3, S18–S21.Google Scholar
Fuller, NJ, Murgatroyd, PR, Golberg, GR, Prentice, AM & Coward, WA (1992) Four compartment model for the assessment of body composition in humans: comparison with alternative methods and evaluation of the density and hydration of fat free mass. Clinical Science 82, 687–693.Google Scholar
Galitzky, J, Lafontan, M, Nordenstrom, J & Arner, P (1993) Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue. Journal of Clinical Investigation 91, 1997–2003.CrossRefGoogle ScholarPubMed
Hacia, JG (1999) Resequencing and mutational analysis using oligonucleotide microarrays. Nature Genetics 21, 42–47.Google Scholar
Havel, PJ (1999) Signals from adipose tissue: regulation of leptin production and energy balance. Journal of Physiology and Biochemistry 55, 106.Google Scholar
Hellerstein, MK (1999) De novo lipogenesis in humans and regulatory aspects. European Journal of Clinical Nutrition 53, 53–65.Google Scholar
Hellerstein, MK, Schwartz, JM & Neese, A (1996) Regulation of hepatic de novo lipogenesis in humans. Annual Review of Nutrition 16, 523–557.Google Scholar
Hesketh, JE & Partridge, K (1996) Gene cloning: studies of nutritional regulation of expression. Proceedings of the Nutrition Society 55, 575–581.Google Scholar
Hu, E, Liang, P & Spiegelman, BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. Journal of Biological Chemistry 71, 10697–10703.CrossRefGoogle Scholar
James, WPT & Ralph, A (1999) New understanding in obesity research. Proceedings of the Nutrition Society 58, 385–393.CrossRefGoogle ScholarPubMed
Jebb, SA (1998) Measurement of body composition – from the laboratory to the clinic. In Clinical Obesity, pp. 18–49 [Koppelman, P and Stock, M, editors]. London: Blackwell.Google Scholar
Jebb, SA, Cole, TJ, Doman, D, Murgatroyd, PR & Prentice, AM (2000) Evaluation of the novel Tanita body-fat analyser to measure body composition by comparison with a four-compartment model. British Journal of Nutrition 83, 115–122.Google Scholar
Jebb, SA, Murgatroyd, PR, Golberg, GR, Prentice, AM & Coward, WA (1993) In vivo measurement of changes in body composition: description of methods and their validation against 12-d continuous whole-body calorimetry. American Journal of Clinical Nutrition 58, 455–462.Google Scholar
Jecquier, E & Tappy, L (1999) Regulation of body weight in humans. Physiological Review 70, 451–480.Google Scholar
Lafontan, M & Arner, P (1996) Application of in situ microdialysis to measure metabolic and vascular responses in adipose tissue. Trends in Pharmacological Science 17, 309–313.Google Scholar
Laville, M, Auboeuf, D, Khalfallah, Y, Vega, N, Riou, JP & Vidal, H (1996) Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle. Journal of Clinical Investigation 98, 43–49.Google Scholar
Lean, MEJ (1999) The pathophysiology of obesity. Journal of Physiology and Biochemistry 55, 114.Google Scholar
Liang, P & Pardee, AB (1998) Differential display. A general protocol. Molecular Biotechnology 10, 261–267.Google Scholar
Lin, X, Braymer, HD, Bray, GA & York, DA (1998) Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity. Life Sciences 63, 145–153.Google Scholar
Marti, A, Novo, FJ, Martinez-Anso, E, Zaratiegui, M, Aguado, M & Martinez, JA (1998) Leptin gene transfer into muscle increases lipolysis and oxygen consumption in white fat tissue in ob/ob mice. Biochemical and Biophysical Research Communications 246, 859–862.Google Scholar
Martinez, JA (1999) Body weight regulation: causes of obesity. Journal of Physiology and Biochemistry 55, 100.Google Scholar
Martinez, JA & Marti, A (1998) Metabolismo lipidico y lipogénesis: aplicación de isotópos estables (Lipid metabolism and lipogenesis: application of stable isotopes). Revista Medicina 42, 91–98.Google Scholar
Montague, CT, Farooqi, IS, Whitehead, P, Soos, MA, Rau, H, Warehams, NJ & Sewter, CP (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903–908.Google Scholar
Morsy, MA, Gu, MC, Motzel, S, Zhao, Z, Lin, J, Su, Q, Allen, H, Franlin, L, Parks, RJ, Graham, FL, Kochamer, S, Bett, AJ & Caskey, CT (1998a) An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene. Proceedings of the National Academy of Sciences USA 95, 7866–7871.Google Scholar
Morsy, MA, Gu, MC, Zhao, JZ, Holder, DJ, Rogers, IT, Pouch, WJ, Motzel, SL, Klein, HJ, Gupta, SK, Liang, X, Tota, MR, Rosenblum, CI & Caskey, CT (1998b) Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mice. Gene Therapy 5, 8–18.Google Scholar
Muzzin, P, Eisensmith, RC, Copeland, KC & Woo, SL (1996) Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. Proceedings of the National Academy of Sciences USA 93, 14804–14808.Google Scholar
Nicholls, DG & Locke, RM (1984) Thermogenic mechanism in brown fat. Physiological Reviews 64, 1–64.Google Scholar
Perusse, L, Chagnon, YC, Weisnagel, J & Bouchard, C (1999) The human obesity gene map: the 1998 update. Obesity Research 7, 111–129.Google Scholar
Pi-Sunyer, FX (1999) Obesity: Criteria and classification. Journal of Physiology and Biochemistry 55, 121.Google Scholar
Poppit, SD, Murgatroyd, PR, Tanish, KR & Prentice, AM (1997) Effect of dexfenfluoramine on energy and macronutrient balance on high-fat and low-fat diets. International Journal of Obesity 21, 197 Abstr.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, 827–833.Google Scholar
Schoeller, DA (1999) Recent advances from application of doubly labeled water to measurement of human energy expenditure. Journal of Nutrition 129, 1765–1768.Google Scholar
Schrauwen, P, Walder, K & Ravussin, E (1999) Human uncoupling proteins and obesity. Obesity Research 7, 97–105.Google Scholar
Schutz, Y (1999) Body weight balance and regulation: role of substrate utilization and thermogenesis. Journal of Physiology and Biochemistry 55, 128.Google Scholar
Schwartz, MW, Baskin, DG, Kayale, KS & Woods, SC (1999) Model for the regulation of energy balance and adiposity by the central nervous system. American Journal of Clinical Nutrition 69, 584–596.CrossRefGoogle ScholarPubMed
Sjostrom, LA (1991) A computer-tomography based multi-compartment body composition technique and anthropometric predictions of lean body mass, total and subcutaneous adipose tissue. International Journal of Obesity 15, 19–30.Google Scholar
Strobel, A, Issad, T, Camoin, L, Ozata, M & Strosberg, AD (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nature Genetics 98, 213–215.Google Scholar
Tappy, L, Schwarz, JM, Schneiter, P, Cayeux, C, Revelly, JP, Fagerquist, CK, Jequier, E & Chiolero, R (1998) Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients. Critical Care Medicine 26, 860–867.Google Scholar
Trayhurn, P (1998) Molecular biology and nutrition: the quest for integration. British Journal of Nutrition 80, 305–306.Google Scholar
Trayhurn, P, Hoggard, N, Mercer, JG & Rayner, DV (1999) Leptin: fundamental aspects. International Journal of Obesity 23, 22–28.CrossRefGoogle ScholarPubMed
Webber, J & Macdonald, I (1999) Signalling in body weight homeostasis: neuroendocrine efferent signals. Journal of Physiology and Biochemistry 55, 124.Google Scholar
Vicent, D, Piper, M, Gammeltoft, S, Maratos-Flier, E & Kahn, CR (1998) Alterations in skeletal muscle gene expression of ob/ob mice by mRNA differential display. Diabetes 47, 1451–1458.Google Scholar
Willett, WC (1999) Is dietary fat a major determinant of body fat? Journal of Physiology and Biochemistry 55, 123.Google Scholar
Williams, G, Harold, JA, Jun, Cai X & Cutler, DJ (1999) Hypothalamic control of energy balance. Journal of Physiology and Biochemistry 55, 104.Google Scholar
Yanovski, JA & Yanovski, SZ (1999) Recent advances in basic obesity research. Journal of the American Medical Association 282, 1054–1056.Google ScholarPubMed
Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.Google Scholar