Hostname: page-component-f554764f5-nqxm9 Total loading time: 0 Render date: 2025-04-13T23:44:29.811Z Has data issue: false hasContentIssue false
  • English
  • Français

Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and peroxisome-proliferator-activated-receptor-γ2 gene polymorphisms

Published online by Cambridge University Press:  08 March 2007

Estibaliz Goyenechea ,
M. Dolores Parra  and
J. Alfredo Martínez
Estibaliz Goyenechea
Affiliation:
Department of Physiology and Nutrition, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain
M. Dolores Parra
Affiliation:
Department of Physiology and Nutrition, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain
J. Alfredo Martínez*
Affiliation:
Department of Physiology and Nutrition, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain
*
*Corresponding author: Professor J. Alfredo Martínez, fax +34 948425649, email [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.

Weight-loss maintenance after following an energy-restricted diet is a major problem that a number of studies are trying to characterise. The aim of the present study was to investigate the role of IL-6 -174G > C and PPAR-γ2 Pro12Ala variants on weight regulation in obese subjects receiving a low-energy diet and at 1 year after the acute slimming period. Sixty-seven volunteers (age 34·7 (sd 7·0) years; BMI 35·8 (sd 4·8) kg/m2) were enrolled in a 10-week dietary intervention and were contacted again 1 year after the end of this period. Body composition was measured at three times during the study. Also, PPAR-γ2 Pro12Ala and IL-6 -174G > C polymorphisms were analysed in the participants. No statistical differences were observed depending on the genetic variants at baseline for anthropometric variables, or after the intervention. However, the C allele of the -174G > C IL-6 gene polymorphism was more frequently observed (P=0·032) in subjects with successful weight maintenance (<10 % weight regain). In fact, the C allele partially protected against weight regain (odds ratio 0·24; P=0·049), while the conjoint presence of both gene variants (C+ and Ala+) further improved the ability for weight maintenance (odds ratio 0·19; P=0·043). The present study demonstrates that the C allele of the -174G > C polymorphism gives protection against regain of weight lost. Moreover, the presence of the Ala allele of the PPARγ-2 together with the C allele strengthens this protection. These findings support a role for these polymorphisms on weight regulation and suggest a synergetic effect of both variants on weight maintenance after following a diet to lose weight.

Keywords

Interleukin-6ObesityWeight lossGene–nutrient interactions
Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 5 , November 2006 , pp. 965 - 972
Copyright
Copyright © The Nutrition Society 2006

References

Abeke, I, Parra, MD & Martinez, JA (2006) Different dietary strategies for weight less in obesity: role of energy and macronutrient content. Nutr Res Rev 19, 1–14.Google Scholar
Aronne, LJ (1998) Obesity. Med Clin North Am 82, 161–181.CrossRefGoogle ScholarPubMed
Auwerx, J (1999) PPARgamma, the ultimate thrifty gene. Diabetologia 42, 1033–1049.CrossRefGoogle ScholarPubMed
Barbieri, M, Rizzo, MR, Papa, M, Acampora, R, De Angelis, L, Olivieri, F, Marchegiani, F, Franceschi, C & Paolisso, G (2005) Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors. Exp Gerontol 40, 599–604.CrossRefGoogle ScholarPubMed
Beamer, BA, Yen, CJ, Andersen, RE, Muller, D, Elahi, D, Cheskin, LJ, Andres, R, Roth, J & Shuldiner, AR (1998) Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes 47, 1806–1808.CrossRefGoogle ScholarPubMed
Berthier, MT, Paradis, AM, Tchernof, A, Bergeron, J, Prud'homme, D, Despres, JP & Vohl, MC (2003) The interleukin 6-174G/C polymorphism is associated with indices of obesity in men. J Hum Genet 48, 14–19.CrossRefGoogle ScholarPubMed
Dedoussis, GV, Manios, Y, Choumerianou, DM, Yiannakouris, N, Panagiotakos, DB, Skenderi, K & Zampelas, A (2004) The IL-6 gene G-174C polymorphism related to health indices in Greek primary school children.Obes Res 12, 1037–1041.CrossRefGoogle ScholarPubMed
Deeb, SS, Fajas, L, Nemoto, M, Pihlajamaki, J, Mykkanen, L, Kuusisto, J, Laakso, M, Fujimoto, W & Auwerx, J (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20, 284–287.CrossRefGoogle ScholarPubMed
Ek, J, Urhammer, SA, Sorensen, TI, Andersen, T, Auwerx, J & Pedersen, O (1999) Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men. Diabetologia 42, 892–895.CrossRefGoogle ScholarPubMed
Fantuzzi, G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115, 911–919.CrossRefGoogle ScholarPubMed
Fernandez-Real, JM, Broch, M, Vendrell, J, Gutierrez, C, Casamitjana, R, Pugeat, M, Richart, C & Ricart, W (2000 a) Interleukin-6 gene polymorphism and insulin sensitivity. Diabetes 49, 517–520.CrossRefGoogle ScholarPubMed
Fernandez-Real, JM, Broch, M, Vendrell, J, Richart, C & Ricart, W (2000 b) Interleukin-6 gene polymorphism and lipid abnormalities in healthy subjects. J Clin Endocrinol Metab 85, 1334–1339.CrossRefGoogle ScholarPubMed
Fishman, D, Faulds, G, Jeffery, R, Mohamed-Ali, V, Yudkin, JS, Humphries, S & Woo, P (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102, 1369–1376.CrossRefGoogle Scholar
Goyenechea, E, Parra, MD & Martinez, JA (2005) Role of IL-6 and its -174G>C polymorphism in weight management and in the metabolic comorbidities associated with obesity. An Sist Sanit Navar 28, 357–366.Google Scholar
Greenwald, A (2006) Current nutritional treatments of obesity. Adv Psychosom Med 27, 24–41.CrossRefGoogle ScholarPubMed
Halverstadt, A, Phares, DA, Roth, S, Ferrell, RE, Goldberg, AP & Hagberg, JM (2005) Interleukin-6 genotype is associated with high-density lipoprotein cholesterol responses to exercise training. Biochim Biophys Acta 1734, 143–151.CrossRefGoogle ScholarPubMed
Hamid, YH, Rose, CS & Urhammer, SA (2005) Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes. Diabetologia 48, 251–260.CrossRefGoogle ScholarPubMed
Hara, K, Kubota, N & Tobe, K (2000) The role of PPARγ as a thrifty gene both in mice and humans. Br J Nutr, 84, Suppl. 2, S235–S239.CrossRefGoogle ScholarPubMed
Humphries, SE, Luong, LA, Ogg, MS, Hawe, E & Miller, GJ (2001) The interleukin-6 -174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 22, 2243–2252.CrossRefGoogle ScholarPubMed
Jiang, C, Ting, AT & Seed, B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82–86.CrossRefGoogle ScholarPubMed
Kubaszek, A, Pihlajamaki, J, Punnonen, K, Karhapaa, P, Vauhkonen, I & Laakso, M (2003) The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity. Diabetes 52, 558–561.CrossRefGoogle ScholarPubMed
Labayen, I, Diez, N, Parra, D, Gonzalez, A & Martinez, JA (2004) Basal and postprandial substrate oxidation rates in obese women receiving two test meals with different protein content. Clin Nutr 23, 571–578.CrossRefGoogle ScholarPubMed
Lachin, JM (2005) A review of methods for futility stopping based on conditional power. Stat Med 24, 2747–2764.CrossRefGoogle ScholarPubMed
Lieb, W, Pavlik, R & Erdmann, J (2004) No association of interleukin-6 gene polymorphism (-174 G/C) with myocardial infarction or traditional cardiovascular risk factors. Int J Cardiol 97, 205–212.CrossRefGoogle ScholarPubMed
Lindi, V, Sivenius, K, Niskanen, L, Laakso, M & Uusitupa, MI (2001) Effect of the Pro12Ala polymorphism of the PPAR-gamma2 gene on long-term weight change in Finnish non-diabetic subjects. Diabetologia 44, 925–926.Google ScholarPubMed
Lindi, VI, Uusitupa, MI, Lindstrom, J, et al. (2002) Association of the Pro12Ala polymorphism in the PPAR–gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study.. Diabetes 51, 2581–;2586.CrossRefGoogle ScholarPubMed
Mancini, FP, Vaccaro, O, Sabatino, L, Tufano, A, Rivellese, AA, Riccardi, G & Colantuoni, V (1999) Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes. Diabetes 48, 1466–1468.CrossRefGoogle Scholar
Marti, A, Corbalan, MS, Martinez-Gonzalez, MA, Forga, L & Martinez, JA (2002) CHO intake alters obesity risk associated with Pro12Ala polymorphism of PPARgamma gene. J Physiol Biochem 58, 219–220.CrossRefGoogle ScholarPubMed
Marti, A, Moreno-Aliaga, MJ, Hebebrand, J & Martinez, JA (2004) Genes, lifestyles and obesity. Int J Obes Relat Metab Disord 28, Suppl. 3, S29–S36.CrossRefGoogle ScholarPubMed
Martinez, JA (2000) Body-weight regulation: causes of obesity. Proc Nutr Soc 59, 337–345.CrossRefGoogle ScholarPubMed
Martinez-Gonzalez, MA, Martinez, JA, Hu, FBGibney, MJ & Keamey, (1999) Physical inactivity, sedentary lifestyle and obesity in the European Union. Int J Obes Relat Metab Disord 23, 1192–1201.CrossRefGoogle ScholarPubMed
Masugi, J, Tamori, Y, Mori, H, Koike, T & Kasuga, M (2000) Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun 268, 178–182.CrossRefGoogle ScholarPubMed
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. J Clin Endocrinol Metab 82, 4196–4200.Google Scholar
Moreno-Aliaga, MJ, Campion, J, Milagro, FI, Berjón, A & Martinez, JA (2005) Adiposity and proinflammatory state: the chicken or the egg. Adipocytes 1, 1–16.Google Scholar
Nicklas, BJ, van Rossum, EF, Berman, DM, Ryan, AS, Dennis, KE & Shuldiner, AR (2001) Genetic variation in the peroxisome proliferator-activated receptor-gamma2 gene (Pro12Ala) affects metabolic responses to weight loss and subsequent weight regain. Diabetes 50, 2172–2176.CrossRefGoogle ScholarPubMed
Ochoa, MC, Marti, A & Azcona, C (2004) Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents. Int J Obes Relat Metab Disord 28, Suppl. 3, S37–S41.CrossRefGoogle ScholarPubMed
Parra, MD, Martinez de Morentin, BE & Martinez, JA (2005) Postprandial insulin response and mitochondrial oxidation in obese men nutritionally treated to lose weight. Eur J Clin Nutr 59, 334–340.CrossRefGoogle ScholarPubMed
Pérez, S, Parra, MD, Martínez de Morentin, B, Rodríguez, MC & Martínez, JA (2005) Evaluación de la variabilidad intraindividual de la medida de composición corporal mediante bioimpedancia en voluntarias sanas y su relación con el índice de masa corporal y el pliegue tricipital (Evaluation of intraindividual variability in the measurement of body composition using electrical bioimpedance in healthy volunteers and its relationship with body mass index and triceps skinfold measurement). Enferm Clin 15, 343–347.CrossRefGoogle Scholar
Poitou, C, Lacorte, JM & Coupaye, M (2005) Relationship between single nucleotide polymorphisms in leptin, IL6 and adiponectin genes and their circulating product in morbidly obese subjects before and after gastric banding surgery. Obes Surg 15, 11–23.CrossRefGoogle ScholarPubMed
Rankinen, T, Zuberi, A, Chagnon, YC, Weisnagel, SJ, Argyropoulos, G, Walts, B, Perusse, L & Bouchard, C (2006) The human obesity gene map: the 2005 update. Obesity 14, 529–644.CrossRefGoogle ScholarPubMed
Ricote, M, Li, AC, Willson, TM, Kelly, CJ & Glass, CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391, 79–82.CrossRefGoogle ScholarPubMed
Sesti, G, Perego, L & Cardellini, M (2005) Impact of common polymorphisms in candidate genes for insulin resistance and obesity on weight loss of morbidly obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet. J Clin Endocrinol Metab 90, 5064–5069.CrossRefGoogle ScholarPubMed
Trayhurn, P & Wood, IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92, 347–355.CrossRefGoogle ScholarPubMed
Trayhurn, P & Wood, IS (2005) Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 33, 1078–1081.CrossRefGoogle ScholarPubMed
Tsigos, C, Papanicolaou, DA, Defensor, R, Mitsiadis, CS, Kyrou, I & Chrousos, GP (1997) Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology 66, 54–62.CrossRefGoogle ScholarPubMed
Vogels, N, Diepvens, K & Westerterp-Plantenga, MS (2005 a) Predictors of long-term weight maintenance. Obes Res 13, 2162–2168.CrossRefGoogle ScholarPubMed
Vogels, N, Mariman, EC, Bouwman, FG, Kester, AD, Diepvens, K & Westerterp-Plantenga, MS (2005 b) Relation of weight maintenance and dietary restraint to peroxisome proliferator-activated receptor gamma2, glucocorticoid receptor, and ciliary neurotrophic factor polymorphisms. Am J Clin Nutr 82, 740–746.CrossRefGoogle ScholarPubMed
Vozarova, B, Fernandez-Real, JM & Knowler, WC (2003) The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in Native Americans and Caucasians. Hum Genet 112, 409–413.CrossRefGoogle ScholarPubMed
Weinsier, RL, Hunter, GR, Desmond, RA, Byrne, NM, Zuckerman, PA & Darnell, BE (2002) Free-living activity energy expenditure in women successful and unsuccessful at maintaining a normal body weight. Am J Clin Nutr 75, 499–504.CrossRefGoogle ScholarPubMed
Wernstedt, I, Eriksson, AL, Berndtsson, A, Hoffstedt, J, Skrtic, S, Hedner, T, Hulten, LM, Wiklund, O, Ohlsson, C & Jansson, JO (2004) A common polymorphism in the interleukin-6 gene promoter is associated with overweight. Int J Obes Relat Metab Disord 28, 1272–1279.CrossRefGoogle ScholarPubMed
Wing, RR & Phelan, S (2005) Long-term weight loss maintenance. Am J Clin Nutr 82 Suppl. 1. S222–S225.CrossRefGoogle ScholarPubMed
Wu, Z, Xie, Y, Bucher, NL & Farmer, SR (1995) Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev 9, 2350–2363.CrossRefGoogle ScholarPubMed
Yen, CJ, Beamer, BA, Negri, C, Silver, K, Brown, KA, Yarnall, DP, Burns, DK, Roth, J & Shuldiner, AR (1997) Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun 241, 270–274.CrossRefGoogle ScholarPubMed