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Altered adipocyte structure and function in nutritionally programmed microswine offspring

Published online by Cambridge University Press:  25 April 2012

E. A. DuPriest ,
P. Kupfer ,
B. Lin ,
K. Sekiguchi ,
T. K. Morgan ,
K. E. Saunders ,
T. T. Chatkupt ,
O. N. Denisenko ,
J. Q. Purnell  and
S. P. Bagby
E. A. DuPriest
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA Department of Natural Sciences and Health, Warner Pacific College, Portland, OR, USA
P. Kupfer
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
B. Lin
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
K. Sekiguchi
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
T. K. Morgan
Affiliation:
Department of Pathology, Oregon Health & Science University, Portland, OR, USA
K. E. Saunders
Affiliation:
Department of Comparative Medicine, Oregon Health & Science University, Portland, OR, USA
T. T. Chatkupt
Affiliation:
Department of Comparative Medicine, Oregon Health & Science University, Portland, OR, USA
O. N. Denisenko
Affiliation:
Department of Medicine, University of Washington, Seattle, WA, USA
J. Q. Purnell
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA
S. P. Bagby*
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
*
*Address for correspondence: Dr S. P. Bagby, Professor of Medicine & Physiology/Pharmacology, Division of Nephrology & Hypertension, Oregon Health & Science University, 3303 SW Bond Avenue (CH12R), Portland, OR 97239-3098, USA. Email [email protected]
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Abstract

Adipose tissue (AT) dysfunction links obesity of any cause with cardiometabolic disease, but whether early-life nutritional deficiency can program adipocyte dysfunction independently of obesity is untested. In 3–5-month-old juvenile microswine offspring exposed to isocaloric perinatal maternal protein restriction (MPR) and exhibiting accelerated prepubertal fat accrual without obesity, we assessed markers of acquired obesity: adiponectin and tumor necrosis factor (TNF)-α messenger ribonucleic acid (mRNA) levels and adipocyte size in intra-abdominal (ABD-AT) and subcutaneous (SC-AT) adipose tissues. Plasma cortisol, leptin and insulin levels were measured in fetal, neonatal and juvenile offspring. In juvenile low-protein offspring (LPO), adipocyte size in ABD-AT was reduced 22% (P = 0.011 v. controls), whereas adipocyte size in SC-AT was increased in female LPO (P = 0.05) and normal in male LPO; yet, adiponectin mRNA in LPO was low in both sexes and in both depots (P < 0.001). Plasma leptin (P = 0.004) and cortisol (P < 0.05) were reduced only in neonatal LPO during MPR. In juveniles, correlations between % body fat and adiponectin mRNA, TNF-α mRNA or plasma leptin were significant in normal-protein offspring (NPO) but absent in LPO. Plasma glucose in juvenile LPO was increased in males but decreased in females (interaction, P = 0.023); plasma insulin levels and insulin sensitivity were unaffected. Findings support nutritional programming of adipocyte size and gene expression and subtly altered glucose homeostasis. Reduced adiponectin mRNA and adipokine dysregulation in juvenile LPO following accelerated growth occurred independently of obesity, adipocyte hypertrophy or inflammatory markers; thus, perinatal MPR and/or growth acceleration can alter adipocyte structure and disturb adipokine homeostasis in metabolically adverse patterns predictive of enhanced disease risk.

Keywords

adipose tissuecatch-up growthmaternal protein restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 3 , June 2012 , pp. 198 - 209
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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References

1. Fall, CH, Osmond, C, Barker, DJ, et al. . Fetal and infant growth and cardiovascular risk factors in women. BMJ. 1995; 310, 428–432.CrossRefGoogle ScholarPubMed
2. Mi, J, Law, C, Zhang, KL, et al. . Effects of infant birthweight and maternal body mass index in pregnancy on components of the insulin resistance syndrome in China. Ann Intern Med. 2000; 132, 253–260.CrossRefGoogle ScholarPubMed
3. Curhan, GC, Willett, WC, Rimm, EB, et al. . Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation. 1996; 94, 3246–3250.Google Scholar
4. Curhan, GC, Chertow, GM, Willett, WC, et al. . Birth weight and adult hypertension and obesity in women. Circulation. 1996; 94, 1310–1315.CrossRefGoogle ScholarPubMed
5. Eriksson, J, Forsen, T, Tuomilehto, J, Osmond, C, Barker, D. Fetal and childhood growth and hypertension in adult life. Hypertension. 2000; 36, 790–794.Google Scholar
6. Barker, DJP, Bull, AR, Osmond, C, Simmonds, SJ. Fetal and placental size and risk of hypertension in later life. BMJ. 1990; 301, 259–262.Google Scholar
7. de Ferranti, S, Mozaffarian, D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008; 54, 945–955.CrossRefGoogle ScholarPubMed
8. Arita, Y, Kihara, S, Ouchi, N, et al. . Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999; 257, 79–83.CrossRefGoogle ScholarPubMed
9. Engeli, S, Feldpausch, M, Gorzelniak, K, et al. . Association between adiponectin and mediators of inflammation in obese women. Diabetes. 2003; 52, 942–947.Google Scholar
10. Kalil, GZ, Haynes, WG. Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. Hypertens Res. 2012; 35, 4–16.CrossRefGoogle ScholarPubMed
11. Weisberg, SP, McCann, D, Desai, M, et al. . Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003; 112, 1796–1808.CrossRefGoogle ScholarPubMed
12. Gallagher, EJ, Leroith, D, Karnieli, E. Insulin resistance in obesity as the underlying cause for the metabolic syndrome. Mt Sinai J Med. 2010; 77, 511–523.CrossRefGoogle ScholarPubMed
13. Clark, PM. Programming of the hypothalamo–pituitary–adrenal axis and the fetal origins of adult disease hypothesis. Eur J Pediatr. 1998; 157(Suppl. 1), S7–S10.CrossRefGoogle ScholarPubMed
14. Reynolds, RM. Corticosteroid-mediated programming and the pathogenesis of obesity and diabetes. J Steroid Biochem Mol Biol. 2010; 122, 3–9.Google Scholar
15. DuPriest, EA, Kupfer, P, Lin, B, et al. . Accelerated growth without prepubertal obesity in nutritionally programmed microswine offspring. J DOHaD. 2012; 3(2): 92–102.Google ScholarPubMed
16. Widdowson, EM. Chemical composition of newly born mammals. Nature. 1950; 166, 626–628.Google Scholar
17. Widdowson, EM. Food intake and growth in the newly-born. Proc Nutr Soc. 1971; 30, 127–135.Google Scholar
18. Manners, MJ, McCrea, MR. Changes in the chemical composition of sow-reared piglets during the 1st month of life. Br J Nutr. 1963; 17, 495–513.Google Scholar
19. Denisenko, ON, Lin, B, Louey, S, et al. . Maternal malnutrition and placental insufficiency induce global downregulation of gene expression in fetal kidneys. J DOHaD. 2011; 2, 124–133.Google Scholar
20. Bagby, SP, Xue, H, Kupfer, P, et al. . Maternal protein restriction in microswine: food restriction from weaning to prevent excess intake corrects vascular dysfunction in juvenile offspring. Early Hum Dev. 2007; 83(Suppl. 1), S87 (Abstract).CrossRefGoogle Scholar
21. DuPriest, EA, Kupfer, P, Lin, B, et al. . Prevention of accelerated growth in nutritionally programmed offspring does not ameliorate adipose tissue dysfunction. J DOHaD. 2011; 2(Suppl S1), S128–S129.Google Scholar
22. Katz, A, Nambi, SS, Mather, K, et al. . Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000; 85, 2402–2410.Google Scholar
23. Wake, DJ, Rask, E, Livingstone, DE, et al. . Local and systemic impact of transcriptional up-regulation of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue in human obesity. J Clin Endocrinol Metab. 2003; 88, 3983–3988.CrossRefGoogle Scholar
24. Spurlock, ME, Gabler, NK. The development of porcine models of obesity and the metabolic syndrome. J Nutr. 2008; 138, 397–402.CrossRefGoogle ScholarPubMed
25. Wernersson, R, Schierup, MH, Jorgensen, FG, et al. . Pigs in sequence space: a 0.66X coverage pig genome survey based on shotgun sequencing. BMC Genomics. 2005; 6, 70.CrossRefGoogle ScholarPubMed
26. Trayhurn, P, Temple, NJ, Van, AJ. Evidence from immunoblotting studies on uncoupling protein that brown adipose tissue is not present in the domestic pig. Can J Physiol Pharmacol. 1989; 67, 1480–1485.CrossRefGoogle Scholar
27. Berg, F, Gustafson, U, Andersson, L. The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: a genetic explanation for poor thermoregulation in piglets. PLoS Genet. 2006; 2, e129.Google Scholar
28. Knittle, JL, Timmers, K, Ginsberg-Fellner, F, Brown, RE, Katz, DP. The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size. J Clin Invest. 1979; 63, 239–246.Google Scholar
29. Isganaitis, E, Jimenez-Chillaron, J, Woo, M, et al. . Accelerated postnatal growth increases lipogenic gene expression and adipocyte size in low-birth weight mice. Diabetes. 2009; 58, 1192–1200.Google Scholar
30. Chumlea, WC, Roche, AF, Siervogel, RM, Knittle, JL, Webb, P. Adipocytes and adiposity in adults. Am J Clin Nutr. 1981; 34, 1798–1803.CrossRefGoogle ScholarPubMed
31. Ozanne, SE, Dorling, MW, Wang, CL, Petry, CJ. Depot-specific effects of early growth retardation on adipocyte insulin action. Horm Metab Res. 2000; 32, 71–75.Google Scholar
32. Yamauchi, T, Kamon, J, Waki, H, et al. . The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem. 2001; 276, 41245–41254.Google Scholar
33. Qiao, L, Lee, B, Kinney, B, Yoo, HS, Shao, J. Energy intake and adiponectin gene expression. Am J Physiol Endocrinol Metab. 2011; 300, E809–E816.Google Scholar
34. Fasshauer, M, Klein, J, Neumann, S, Eszlinger, M, Paschke, R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2002; 290, 1084–1089.CrossRefGoogle ScholarPubMed
35. Fasshauer, M, Kralisch, S, Klier, M, et al. . Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2003; 301, 1045–1050.Google Scholar
36. Tilg, H, Moschen, AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006; 6, 772–783.CrossRefGoogle ScholarPubMed
37. Iwai, M, Kanno, H, Tomono, Y, et al. . Direct renin inhibition improved insulin resistance and adipose tissue dysfunction in type 2 diabetic KK-A(y) mice. J Hypertens. 2010; 28, 1471–1481.Google Scholar
38. Imai, J, Katagiri, H, Yamada, T, et al. . Cold exposure suppresses serum adiponectin levels through sympathetic nerve activation in mice. Obesity (Silver Spring). 2006; 14, 1132–1141.CrossRefGoogle ScholarPubMed
39. Meral, C, Cekmez, F, Pirgon, O, et al. . The relationship between serum visfatin, adiponectin, and insulin sensitivity markers in neonates after birth. J Matern Fetal Neonatal Med. 2011; 24, 166–170.Google Scholar
40. Martos-Moreno, GA, Barrios, V, Saenz de, PM, et al. . Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism. Eur J Endocrinol. 2009; 161, 381–389.Google Scholar
41. Laudes, M, Oberhauser, F, Bilkovski, R, et al. . Human fetal adiponectin and retinol-binding protein (RBP)-4 levels in relation to birth weight and maternal obesity. Exp Clin Endocrinol Diabetes. 2009; 117, 146–149.Google Scholar
42. Gohlke, BC, Bartmann, P, Fimmers, R, et al. . Fetal adiponectin and resistin in correlation with birth weight difference in monozygotic twins with discordant growth. Horm Res. 2008; 69, 37–44.Google Scholar
43. Cianfarani, S, Martinez, C, Maiorana, A, et al. . Adiponectin levels are reduced in children born small for gestational age and are inversely related to postnatal catch-up growth. J Clin Endocrinol Metab. 2004; 89, 1346–1351.Google Scholar
44. Jaquet, D, Deghmoun, S, Chevenne, D, Czernichow, P, Levy-Marchal, C. Low serum adiponectin levels in subjects born small for gestational age: impact on insulin sensitivity. Int J Obes (Lond). 2006; 30, 83–87.Google Scholar
45. Ibanez, L, Lopez-Bermejo, A, Diaz, M, et al. . Abdominal fat partitioning and high-molecular-weight adiponectin in short children born small for gestational age. J Clin Endocrinol Metab. 2009; 94, 1049–1052.Google Scholar
46. Challa, AS, Evagelidou, EN, Cholevas, VI, et al. . Growth factors and adipocytokines in prepubertal children born small for gestational age: relation to insulin resistance. Diabetes Care. 2009; 32, 714–719.Google Scholar
47. Ibanez, L, Sebastiani, G, Lopez-Bermejo, A, et al. . Gender specificity of body adiposity and circulating adiponectin, visfatin, insulin, and insulin growth factor-I at term birth: relation to prenatal growth. J Clin Endocrinol Metab. 2008; 93, 2774–2778.CrossRefGoogle ScholarPubMed
48. Iniguez, G, Soto, N, Avila, A, et al. . Adiponectin levels in the first two years of life in a prospective cohort: relations with weight gain, leptin levels and insulin sensitivity. J Clin Endocrinol Metab. 2004; 89, 5500–5503.Google Scholar
49. Ibanez, L, Lopez-Bermejo, A, Diaz, M, et al. . Abdominal fat partitioning and high-molecular-weight adiponectin in short children born small for gestational age. J Clin Endocrinol Metab. 2009; 94, 1049–1052.Google Scholar
50. Ibanez, L, Lopez-Bermejo, A, Suarez, L, et al. . Visceral adiposity without overweight in children born small for gestational age. J Clin Endocrinol Metab. 2008; 93, 2079–2083.Google Scholar
51. Ibanez, L, Lopez-Bermejo, A, Diaz, M, et al. . High-molecular-weight adiponectin in children born small- or appropriate-for-gestational-age. J Pediatr. 2009; 155, 740–742.Google Scholar
52. Ibanez, L, Lopez-Bermejo, A, Diaz, M, et al. . Abdominal fat partitioning and high-molecular-weight adiponectin in short children born small for gestational age. J Clin Endocrinol Metab. 2009; 94, 1049–1052.Google Scholar
53. Lopez-Bermejo, A, Casano-Sancho, P, Fernandez-Real, JM, et al. . Both intrauterine growth restriction and postnatal growth influence childhood serum concentrations of adiponectin. Clin Endocrinol (Oxf). 2004; 61, 339–346.Google Scholar
54. Jaquet, D, Deghmoun, S, Chevenne, D, Czernichow, P, Levy-Marchal, C. Low serum adiponectin levels in subjects born small for gestational age: impact on insulin sensitivity. Int J Obes (Lond). 2006; 30, 83–87.Google Scholar
55. Guan, H, Arany, E, van Beek, JP, et al. . Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats. Am J Physiol Endocrinol Metab. 2005; 288, E663–E673.Google Scholar
56. George, LA, Zhang, L, Tuersunjiang, N, et al. . Early maternal undernutrition programs increased feed intake, altered glucose metabolism and insulin secretion, and liver function, in aged female offspring. Am J Physiol Regul Integr Comp Physiol. 2012; 302(7): R795–R804.Google Scholar
57. Bertram, C, Trowern, AR, Copin, N, Jackson, AA, Whorwood, CB. The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinol. 2001; 142, 2841–2853.Google Scholar
58. Langley-Evans, SC. Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis. J Hypertens. 1997; 15, 537–544.Google Scholar
59. Langley-Evans, SC, Nwagwu, M. Impaired growth and increased glucocorticoid-sensitive enzyme activities in tissues of rat fetuses exposed to maternal low protein diets. Life Sci. 1998; 63, 605–615.Google Scholar
60. Langley-Evans, SC, Gardner, DS, Jackson, AA. Maternal protein restriction influences the programming of the rat hypothalamic–pituitary–adrenal axis. J Nutr. 1996; 126, 1578–1585.Google Scholar
61. Langley-Evans, SC, Phillips, GJ, Benediktsson, R, et al. . Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. Placenta. 1996; 17, 169–172.Google Scholar
62. McMullen, S, Langley-Evans, SC. Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R85–R90.Google Scholar
63. McMullen, S, Langley-Evans, SC. Sex-specific effects of prenatal low-protein and carbenoxolone exposure on renal angiotensin receptor expression in rats. Hypertension. 2005; 46, 1374–1380.Google Scholar
64. Edwards, LJ, McMillen, IC. Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation. Biol Reprod. 2002; 66, 1562–1569.CrossRefGoogle ScholarPubMed
65. Gardner, DS, Jackson, AA, Langley-Evans, SC. The effect of prenatal diet and glucocorticoids on growth and systolic blood pressure in the rat. Proc Nutr Soc. 1998; 57, 235–240.Google Scholar
66. Gnanalingham, MG, Mostyn, A, Symonds, ME, Stephenson, T. Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2. Am J Physiol Regul Integr Comp Physiol. 2005; 289, R1407–R1415.CrossRefGoogle ScholarPubMed
67. Symonds, ME, Gopalakrishnan, G, Bispham, J, et al. . Maternal nutrient restriction during placental growth, programming of fetal adiposity and juvenile blood pressure control. Arch Physiol Biochem. 2003; 111, 45–52.Google Scholar
68. Phillips, DI, Walker, BR, Reynolds, RM, et al. . Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. Hypertension. 2000; 35, 1301–1306.CrossRefGoogle ScholarPubMed
69. Phillips, DI, Barker, DJ, Fall, CH, et al. . Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome? J Clin Endocrinol Metab. 1998; 83, 757–760.Google Scholar
70. Klemcke, HG, Lunstra, DD, Brown-Borg, HM, Borg, KE, Christenson, RK. Association between low birth weight and increased adrenocortical function in neonatal pigs. J Anim Sci. 1993; 71, 1010–1018.Google Scholar
71. Poore, KR, Fowden, AL. The effect of birth weight on hypothalamo-pituitary-adrenal axis function in juvenile and adult pigs. J Physiol. 2003; 547, 107–116.Google Scholar
72. Weaver, SA, Aherne, FX, Meaney, MJ, Schaefer, AL, Dixon, WT. Neonatal handling permanently alters hypothalamic–pituitary–adrenal axis function, behaviour, and body weight in boars. J Endocrinol. 2000; 164, 349–359.Google Scholar