Hostname: page-component-76fb5796d-dfsvx Total loading time: 0 Render date: 2024-04-26T22:46:28.143Z Has data issue: false hasContentIssue false
  • English
  • Français

Prenatal programming of obesity in a swine model of leptin resistance: modulatory effects of controlled postnatal nutrition and exercise

Published online by Cambridge University Press:  26 March 2014

A. Barbero ,
S. Astiz ,
C. Ovilo ,
C. J. Lopez-Bote ,
M. L. Perez-Solana ,
M. Ayuso ,
I. Garcia-Real  and
A. Gonzalez-Bulnes
A. Barbero
Affiliation:
Universidad Complutense de Madrid, Facultad de Veterinaria, Madrid, Spain
S. Astiz
Affiliation:
Animal Reproduction Department, INIA, Madrid, Spain
C. Ovilo
Affiliation:
Animal Reproduction Department, INIA, Madrid, Spain
C. J. Lopez-Bote
Affiliation:
Universidad Complutense de Madrid, Facultad de Veterinaria, Madrid, Spain
M. L. Perez-Solana
Affiliation:
Animal Reproduction Department, INIA, Madrid, Spain
M. Ayuso
Affiliation:
Universidad Complutense de Madrid, Facultad de Veterinaria, Madrid, Spain
I. Garcia-Real
Affiliation:
Universidad Complutense de Madrid, Facultad de Veterinaria, Madrid, Spain
A. Gonzalez-Bulnes*
Affiliation:
Animal Reproduction Department, INIA, Madrid, Spain
*
*Address for correspondence: A. Gonzalez-Bulnes, Animal Reproduction Department, INIA, Avda. Puerta de Hierro s/n. 28040-Madrid, Spain. (Email bulnes@inia.es)
Get access Rights & Permissions [Opens in a new window]

Abstract

The main role of early nutritional programming in the current rise of obesity and associated diseases is well known. However, translational studies are mostly based in postnatal food excess and, thus, there is a paucity of information on the phenotype of individuals with prenatal deficiencies but adequate postnatal conditions. Thus, we assessed the effects of prenatal programming (comparing descendants from females fed with a diet fulfilling 100 or only 50% of their nutritional requirements for pregnancy) on gene expression, patterns of growth and fattening, metabolic status and puberty attainment of a swine model of obesity/leptin resistance with controlled postnatal nutrition and opportunity of exercise. Maternal restriction was related to changes in the relationships among gene expression of positive (insulin-like growth factors 1 and 2) and negative (myostatin) regulators of muscle growth, with negative correlations in gilts from restricted pregnancies and positive relationships in the control group. In spite of these differences, the patterns of growth and fattening and the metabolic features during juvenile growth were similar in control gilts and gilts from restricted pregnancies. Concomitantly, there was a lack of differences in the timing of puberty attainment. However, after reaching puberty and adulthood, females from restricted pregnancies were heavier and more corpulent than control gilts, though such increases in weight and size were not accompanied by increases in adiposity. In conclusion, in spite of changes in gene expression induced by developmental programming, the propensity for higher weight and adiposity of individuals exposed to prenatal malnutrition may be modulated by controlled food intake and opportunity of physical exercise during infant and juvenile development.

Keywords

developmental programmingmetabolismobesity
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 5 , Issue 3 , June 2014 , pp. 248 - 258
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Scully, T. Diabetes in numbers. Nature. 2012; 485, S2–S3.CrossRefGoogle ScholarPubMed
2. Shetty, P. Public health: India’s diabetes time bomb. Nature. 2012; 485, S14–S16.Google Scholar
3. Mohan, M, Prasad, SR, Chellani, HK, Kapani, V. Intrauterine growth curves in north Indian babies: weight, length, head circumference and ponderal index. Indian Pediatr. 1990; 27, 43–51.Google Scholar
4. Bavdekar, A, Yajnik, CS, Fall, CH, et al. Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? Diabetes. 1999; 48, 2422–2429.Google Scholar
5. Krishnaveni, GV, Veena, SR, Dhube, A, et al. Size at birth, morning cortisol and cardiometabolic risk markers in healthy Indian children. Clin Endocrinol. 2014; 80, 73–79.CrossRefGoogle ScholarPubMed
6. Flynn, MA, McNeil, DA, Maloff, B, et al. Reducing obesity and related chronic disease risk in children and youth: a synthesis of evidence with ‘best practice’ recommendations. Obes Rev. 2006; 7, 7–66.Google Scholar
7. Li, P, Yang, F, Xiong, F, et al. Nutritional status and risk factors of overweight and obesity for children aged 9–15 years in Chengdu, Southwest China. BMC Public Health. 2012; 12, 636.Google Scholar
8. Al-Haddad, FH, Little, BB, Abdul Ghafoor, AG. Childhood obesity in United Arab Emirates schoolchildren: a national study. Ann Hum Biol. 2005; 32, 72–79.CrossRefGoogle ScholarPubMed
9. Al-Junaibi, A, Abdulle, A, Sabri, S, Hag-Ali, M, Nagelkerke, N. The prevalence and potential determinants of obesity among school children and adolescents in Abu Dhabi, United Arab Emirates. Int J Obes (Lond). 2013; 37, 68–74.Google Scholar
10. Gluckman, PD, Hanson, MA. Living with the past: evolution, development, and patterns of disease. Science. 2004; 305, 1733–1736.Google Scholar
11. Potenza, MA, Nacci, C, Gagliardi, S, Montagnani, M. Cardiovascular complications in diabetes: lessons from animal models. Curr Med Chem. 2011; 18, 1806–1819.Google Scholar
12. Bähr, A, Wolf, E. Domestic animal models for biomedical research. Reprod Domest Anim. 2012; 47, 59–71.Google Scholar
13. Douglas, WR. Of pigs and men and research: a review of applications and analogies of the pig, Sus scrofa, in human medical research. Space Life Sci. 1972; 3, 226–234.Google Scholar
14. Houpt, KA, Houpt, TR, Pond, WG. The pig as a model for the study of obesity and of control of food intake: a review. Yale J Biol Med. 1979; 52, 307–329.Google Scholar
15. Spurlock, ME, Gabler, NK. The development of porcine models of obesity and the metabolic syndrome. J Nutr. 2008; 138, 397–402.Google Scholar
16. Torres-Rovira, L, Astiz, S, Caro, A, et al. Diet-induced swine model with obesity/leptin resistance for the study of metabolic syndrome and type 2 diabetes. Sci World J. 2012; 2012, Article no. 510149.Google Scholar
17. Torres-Rovira, L, Gonzalez-Añover, P, Astiz, S, et al. Effect of an obesogenic diet during the juvenile period on growth pattern, fatness and metabolic, cardiovascular and reproductive features of swine with obesity/leptin resistance. Endocr Metab Immune Disord Drug Targets. 2013; 13, 143–151.Google Scholar
18. Myers, MG, Cowley, MA, Munzberg, H. Mechanisms of leptin action and leptin resistance. Ann Rev Physiol. 2008; 70, 537–556.CrossRefGoogle ScholarPubMed
19. Lubis, AR, Widia, F, Soegondo, S, Setiawati, A. The role of SOCS-3 protein in leptin resistance and obesity. Acta Med Indones. 2008; 40, 89–95.Google Scholar
20. Mizuta, E, Kokubo, Y, Yamanaka, I, et al. Leptin gene and leptin receptor gene polymorphisms are associated with sweet preference and obesity. Hypertension Res. 2008; 31, 1069–1077.Google Scholar
21. Ovilo, C, Fernández, A, Noguera, JL, et al. Fine mapping of porcine chromosome 6 QTL and LEPR effects on body composition in multiple generations of an Iberian by Landrace intercross. Genet Res. 2005; 85, 57–67.Google Scholar
22. Muñoz, G, Ovilo, C, Silió, L, et al. Single and joint population analyses of two experimental pig crosses to confirm QTL on SSC6 and LEPR effects on fatness and growth traits. J Anim Sci. 2009; 87, 459–468.Google Scholar
23. Gonzalez-Bulnes, A, Ovilo, C, Lopez-Bote, CJ, et al. Gender-specific early postnatal catch-up growth after intrauterine growth retardation by food restriction in swine with obesity/leptin resistance. Reproduction. 2012; 144, 269–278.Google Scholar
24. Gonzalez-Bulnes, A, Ovilo, C, Lopez-Bote, CJ, et al. Fetal and early-postnatal developmental patterns of obese-genotype piglets exposed to prenatal programming by maternal over- and undernutrition. Endocr Metab Immune Disord Drug Targets. 2013; 13, 240–249.Google Scholar
25. Ovilo, C, Gonzalez-Bulnes, A, Benitez, R, et al. Prenatal programming in an obese swine model: sex-related effects of maternal caloric restriction on morphology, metabolism and hypothalamic gene expression. Br J Nutr. 2014; 111, 735–746.Google Scholar
26. Doustmohammadian, A, Abdollahi, M, Bondarianzadeh, D, Houshiarrad, A, Abtahi, M. Parental determinants of overweight and obesity in Iranian adolescents: a national study. Iran J Pediatr. 2012; 22, 35–42.Google Scholar
27. Slyper, AH. Childhood obesity, adipose tissue distribution, and the pediatric practitioner. Pediatrics. 1998; 102, e4.CrossRefGoogle ScholarPubMed
28. Kaplowitz, PB. Link between body fat and the timing of puberty. Pediatrics. 2008; 121, S208–S217.CrossRefGoogle ScholarPubMed
29. Gonzalez-Bulnes, A, Pallares, P, Ovilo, C. Ovulation, implantation and placentation in females with obesity and metabolic disorders: life in the balance. Endocr Metab Immune Disord Drug Targets. 2011; 11, 285–301.Google Scholar
30. Nature Med . Adding fat to the fire. Nature Med. 2013; 19, 947.Google Scholar
31. Jones, KL, Arslanian, S, Peterokova, VA, Park, JS, Tomlinson, MJ. Effect of metformin in pediatric patients with T2DM: a randomized controlled trial. Diabetes Care. 2002; 25, 89–94.Google Scholar
32. Christensen, ML, Rashed, SM, Sinclair, J, et al. Type 2 diabetes mellitus in children and adolescents: the new challenge. J Pediatr Pharmacol Ther. 2004; 9, 15–26.Google Scholar
33. Nicoletto, SF, Rinaldi, A. In the womb’s shadow. The theory of prenatal programming as the fetal origin of various adult diseases is increasingly supported by a wealth of evidence. EMBO Rep. 2011; 12, 30–34.Google Scholar
34. Fisher, RE, Steele, M, Karrow, NA. Fetal programming of the neuroendocrine-immune system and metabolic disease. J Pregnancy. 2012; 2012, 792934.Google Scholar
35. Vignini, A, Raffaelli, F, Cester, A, et al. Environmental and genetical aspects of the link between pregnancy, birth size, and type 2 diabetes. Curr Diabetes Rev. 2012; 8, 155–161.Google Scholar
36. Dyson, MC, Alloosh, M, Vuchetich, JP, Mokelke, EA, Sturek, M. Components of metabolic syndrome and coronary artery disease in female Ossabaw swine fed excess atherogenic diet. Comp Med. 2006; 56, 35–45.Google ScholarPubMed
37. Witczak, CA, Mokelke, EA, Boullion, R, et al. Noninvasive measures of body fat percentage in male Yucatan swine. Comp Med. 2005; 55, 445–451.Google Scholar
38. Christoffersen, BO, Grand, N, Golozoubova, V, Svendsen, O, Raun, K. Gender-associated differences in metabolic syndrome-related parameters in Göttingen minipigs. Comp Med. 2007; 57, 493–504.Google Scholar
39. Mitchell, AD, Scholtz, AM, Wange, PC, Song, H. Body composition analysis of the pig by magnetic resonance imaging. J Anim Sci. 2001; 79, 1800–1813.Google Scholar
40. Matthews, DR, Hosker, JP, Rudenski, AS, et al. Homeostasis model assessment: insulin resistance and B-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28, 412–419.Google Scholar
41. Wallace, TM, Levy, JC, Matthews, DR. Use and abuse of HOMA modeling. Diabetes Care. 2004; 27, 1487–1495.Google Scholar
42. Flowers, B, Cantley, TC, Martin, MJ, Day, BN. Effect of elevated ambient temperatures on puberty in gilts. J Anim Sci. 1989; 67, 779–784.CrossRefGoogle ScholarPubMed
43. Ueshiba, H, Zerah, M, New, MI. Enzyme-linked immunosorbent assay (ELISA). Method for screening of nonclassical steroid 21-hydroxylase deficiency. Norm Metab Res. 1994; 26, 43–45.Google Scholar
44. Gonzalez-Añover, P, Encinas, T, Gomez-Izquierdo, E, et al. Advanced onset of puberty in gilts of thrifty genotype (Iberian pig). Reprod Dom Anim. 2010; 45, 1003–1007.Google Scholar
45. Segura, J, Lopez-Bote, CJ. A laboratory efficient method for intramuscular fat analysis. Food Chem. 2014; 145, 821–825.CrossRefGoogle ScholarPubMed
46. Sukhija, PS, Palmquist, DL. Rapid method for determination of total fatty acid content and composition of feedstuffs and feces. J Agric Food Chem. 1988; 36, 1202–1206.Google Scholar
47. Rey, AI, López-Bote, CJ, Sanz Arias, R. Effect of extensive feeding on α-tocopherol concentration and oxidative stability of muscle microsomes from Iberian pigs. Anim Sci. 1997; 65, 515–520.Google Scholar
48. Guernec, A, Berri, C, Chevalier, B, et al. Muscle development, insulin-like growth factor-I and myostatin mRNA levels in chickens selected for increased breast muscle yield. Growth Horm IGF Res. 2003; 13, 8–18.Google Scholar
49. Stinckens, A, Luyten, T, Van den Maagdenberg, K, et al. Interactions between genes involved in growth and muscularity in pigs: IGF-2, myostatin, ryanodine receptor 1, and melanocortin-4 receptor. Dom Anim Endocrinol. 2009; 37, 227–235.Google Scholar
50. Williams, NG, Interlichia, JP, Jackson, MF, et al. Endocrine actions of myostatin: systemic regulation of the IGF and IGF binding protein axis. Endocrinology. 2011; 152, 172–180.Google Scholar
51. Bayol, S, Jones, D, Goldspink, G, Stickland, NC. The influence of undernutrition during gestation on skeletal muscle cellularity and on the expression of genes that control muscle growth. Br J Nutr. 2004; 91, 331–339.Google Scholar
52. de Moura, LP, Sponton, AC, de Araújo, MB, et al. Moderate physical activity from childhood contributes to metabolic health and reduces hepatic fat accumulation in adult rats. Lipids Health Dis. 2013; 12, 29.Google Scholar
53. Gauthier, MS, Couturier, K, Charbonneau, A, Lavoie, JM. Effects of introducing physical training in the course of a 16-week high-fat diet regimen on hepatic steatosis, adipose tissue fat accumulation, and plasma lipid profile. Int J Obes Relat Metab Disord. 2004; 28, 1064–1071.Google Scholar
54. Hills, AP, Andersen, LB, Byrne, NM. Physical activity and obesity in children. Br J Sports Med. 2011; 45, 866–870.Google Scholar
55. Nettle, H, Sprogis, E. Pediatric exercise: truth and/or consequences. Sports Med Arthrosc. 2011; 19, 75–80.Google Scholar
56. Ibañez, L, de Zegher, F. Puberty after prenatal growth restraint. Hormone Res. 2006; 65, 112–115.CrossRefGoogle ScholarPubMed
57. Sloboda, DM, Hart, R, Doherty, DA, Pennell, CE, Hickey, M. Age at menarche: influences of prenatal and postnatal growth. J Clin Endocrinol Metabol. 2007; 92, 46–50.Google Scholar
58. Hernandez, MI, Mericq, V. Impact of being born small for gestational age on onset and progression of puberty. Best Pract Res Clin Endocrinol Metab. 2008; 22, 463–476.Google Scholar
59. Michalakis, K, Mintziori, G, Kaprara, A, Tarlatzis, BC, Goulis, DG. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism. 2013; 62, 457–478.CrossRefGoogle ScholarPubMed
60. Gardner, DS, Ozanne, SE, Sinclair, KD. Effect of the early-life nutritional environment on fecundity and fertility of mammals. Philos Trans R Soc Lond B Biol Sci. 2009; 364, 3419–3427.Google Scholar
61. Elder, DA, Prigeon, RL, Wadwa, RP, Dolan, LM, D’Alessio, DA. Beta-cell function, insulin sensitivity, and glucose tolerance in obese diabetic and nondiabetic adolescents and young adults. J Clin Endocrinol Metab. 2006; 91, 185–191.Google Scholar
62. Scheen, AJ. Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia. Diabetes Metab. 2010; 36, 31–38.Google Scholar
63. McPherron, AC, Guo, T, Bond, ND, Gavrilova, O. Increasing muscle mass to improve metabolism. Adipocyte. 2013; 2, 92–98.Google Scholar
64. Attie, AD, Krauss, RM, Gray-Keller, MP, et al. Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J Lipid Res. 2002; 43, 1899–1907.Google Scholar
65. Yee, JK, Phillips, SA, Allamehzadeh, K, Herbst, KL. Subcutaneous adipose tissue fatty acid desaturation in adults with and without rare adipose disorders. Lipids Health Dis. 2012; 11, 19.CrossRefGoogle ScholarPubMed
66. Poudyal, H, Brown, L. Stearoyl-CoA desaturase: a vital checkpoint in the development and progression of obesity. Endocr Metab Immune Disord Drug Targets. 2011; 11, 217–231.Google Scholar
67. Hulver, MW, Berggren, JR, Carper, MJ, et al. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab. 2005; 2, 251–261.Google Scholar
68. Warensjo, E, Ohrvall, M, Vessby, B. Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women. Nutr Metab Cardiovasc Dis. 2006; 16, 128–136.Google Scholar
69. Paillard, F, Catheline, D, Duff, FL, et al. Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an independent marker of triglyceridemia and abdominal adiposity. Nutr Metab Cardiovasc Dis. 2008; 18, 436–440.Google Scholar