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Circulating levels of the cytokines IL10, IFNγ and resistin in an obese mouse model of developmental programming

Published online by Cambridge University Press:  24 June 2013

M. A. Kępczyńska ,
E. T. Wargent ,
M. A. Cawthorne ,
J. R. S. Arch ,
J. F. O'Dowd  and
C. J. Stocker
M. A. Kępczyńska
Affiliation:
Clore Laboratory, University of Buckingham, Buckingham, UK
E. T. Wargent
Affiliation:
Clore Laboratory, University of Buckingham, Buckingham, UK
M. A. Cawthorne
Affiliation:
Clore Laboratory, University of Buckingham, Buckingham, UK
J. R. S. Arch
Affiliation:
Clore Laboratory, University of Buckingham, Buckingham, UK
J. F. O'Dowd
Affiliation:
Clore Laboratory, University of Buckingham, Buckingham, UK
C. J. Stocker*
Affiliation:
Clore Laboratory, University of Buckingham, Buckingham, UK
*
*Address for correspondence: C. Stocker, Clore Laboratory, University of Buckingham, Hunter Street, Buckingham MK18 1EG, UK. (Email [email protected])
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Abstract

An infant's early developmental environment plays a pivotal role in the programming of its physiological phenotype. The identification of the factors in the maternal environment that mediate the effects of maternal obesity and diet is essential to the development of clinical intervention strategies. Maternal hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, hyperleptinaemia and altered inflammatory cytokines concentrations are potentially important predictive factors of her future offspring's susceptibility to metabolic disease. Using a diet-induced obese mouse model, we have investigated which of these maternal factors could induce adverse metabolic programming in the offspring. Female C57Bl/6 mice were fed either laboratory chow (10% fat) or high fat diet (42% fat) for 10 weeks before mating and throughout gestation. At day 18 of pregnancy, maternal body weight, body composition and glucose tolerance were measured, as well as plasma insulin, adiponectin, RBP4, leptin, resistin and the inflammatory cytokines (IL6, IL10, IL12, IL1β, IFNγ, KC, TNF-α). At day 18 of pregnancy, high fat-fed dams were significantly heavier than the chow dams and had increased fat mass. High fat-fed dams had higher 5 h fasting blood glucose than chow dams and elevated plasma insulin. Although the obese dams had both reduced plasma adiponectin and resistin levels compared with lean dams, their plasma IL6, IL10 and IFNγ levels were all increased. High fat feeding in pregnancy leads to altered plasma concentrations of both adipokines and adipocytokines in the dam that may directly pass to the fetus and affect their development.

Keywords

cytokinesdevelopmental programmingmaternal obesitymetabolic diseaseovernutrition
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 6 , December 2013 , pp. 491 - 498
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

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References

1.Franks, PW, Hanson, RL, Knowler, WC, et al. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med. 2010; 362, 485–493.CrossRefGoogle ScholarPubMed
2.Whitaker, RC, Wright, JA, Pepe, MS, Seidel, KD, Dietz, WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med. 1997; 337, 869–873.Google Scholar
3.Catalano, PM, Farrell, K, Thomas, A, et al. Perinatal risk factors for childhood obesity and metabolic dysregulation. Am J Clin Nutr. 2009; 90, 1303–1313.Google Scholar
4.Whitaker, KL, Jarvis, MJ, Beeken, RJ, Boniface, D, Wardle, J. Comparing maternal and paternal intergenerational transmission of obesity risk in a large population-based sample. Am J Clin Nutr. 2010; 91, 1560–1567.Google Scholar
5.Pirkola, J, Pouta, A, Bloigu, A, et al. Risks of overweight and abdominal obesity at age 16 years associated with prenatal exposures to maternal prepregnancy overweight and gestational diabetes mellitus. Diabetes Care. 2010; 33, 1115–1121.Google Scholar
6.Koupil, I, Toivanen, P. Social and early-life determinants of overweight and obesity in 18-year-old Swedish men. Int J Obes (Lond). 2008; 32, 73–81.Google Scholar
7.Mingrone, G, Manco, M, Mora, ME, Guidone, C, Iaconelli, A, Gniuli, D, Leccesi, L, Chiellini, C, Ghirlanda, G. Influence of maternal obesity on insulin sensitivity and secretion in the offspring. Diabetes Care. 2008; 31, 1872–1876.Google Scholar
8.Reynolds, RM, Osmond, C, Phillips, DI, Godfrey, KM. Maternal BMI, parity, and pregnancy weight gain: influences on offspring adiposity in young adulthood. J Clin Endocrinol Metab. 2010; 95, 5365–5369.CrossRefGoogle ScholarPubMed
9.Lawlor, DA, Smith, GD, O'Callaghan, M, et al. Epidemiologic evidence for the fetal overnutrition hypothesis: findings from the mater-university study of pregnancy and its outcomes. Am J Epidemiol. 2007; 165, 418–424.Google Scholar
10.Nelson, SM, Matthews, P, Poston, L. Maternal metabolism and obesity: modifiable determinants of pregnancy outcome. Hum Reprod Update. 2010; 16, 255–275.Google Scholar
11.Dabelea, D. The predisposition to obesity and diabetes in offspring of diabetic mothers. Diabetes Care. 2007; 30(Suppl 2), S169–S174.Google Scholar
12.Hillier, TA, Pedula, KL, Schmidt, MM, et al. Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. Diabetes Care. 2007; 30, 2287–2292.Google Scholar
13.Hyperglycemia and Adverse Pregnancy Outcome (HAPO). Study: associations with neonatal anthropometrics. Diabetes. 2009; 58, 453–459.Google Scholar
14.Silverman, BL, Metzger, BE, Cho, NH, Loeb, CA. Impaired glucose tolerance in adolescent offspring of diabetic mothers. Relationship to fetal hyperinsulinism. Diabetes Care. 1995; 18, 611–617.Google Scholar
15.Herrera, E, Amusquivar, E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000; 16, 202–210.Google Scholar
16.Hamilton, JK, Odrobina, E, Yin, J, et al. Maternal insulin sensitivity during pregnancy predicts infant weight gain and adiposity at 1 year of age. Obesity (Silver Spring). 2010; 18, 340–346.Google Scholar
17.Stocker, CJ, Cawthorne, MA. The influence of leptin on early life programming of obesity. Trends Biotechnol. 2008; 26, 545–551.Google Scholar
18.Briana, DD, Malamitsi-Puchner, A. The role of adipocytokines in fetal growth. Ann N Y Acad Sci. 2010; 1205, 82–87.Google Scholar
19.Heerwagen, MJ, Miller, MR, Barbour, LA, Friedman, JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 2010; 299, R711–R722.Google Scholar
20.Poston, L. Developmental programming and diabetes – the human experience and insight from animal models. Best Pract Res Clin Endocrinol Metab. 2010; 24, 541–552.Google Scholar
21.Bayol, SA, Simbi, BH, Bertrand, JA, Stickland, NC. Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J Physiol. 2008; 586, 3219–3230.Google Scholar
22.Nivoit, P, Morens, C, Van Assche, FA, et al. Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance. Diabetologia. 2009; 52, 1133–1142.Google Scholar
23.Samuelsson, AM, Matthews, PA, Argenton, M, et al. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008; 51, 383–392.CrossRefGoogle ScholarPubMed
24.Plagemann, A, Harder, T, Kohlhoff, R, Rohde, W, Dorner, G. Overweight and obesity in infants of mothers with long-term insulin-dependent diabetes or gestational diabetes. Int J Obes Relat Metab Disord. 1997; 21, 451–456.Google Scholar
25.Farley, D, Tejero, ME, Comuzzie, AG, et al. Feto-placental adaptations to maternal obesity in the baboon. Placenta. 2009; 30, 752–760.Google Scholar
26.Strakovsky, RS, Pan, YX. A decrease in DKK1, a WNT inhibitor, contributes to placental lipid accumulation in an obesity-prone rat model. Biol Reprod. 2012; 86, 81.Google Scholar
27.McCurdy, CE, Bishop, JM, Williams, SM, et al. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest. 2009; 119, 323–335.Google ScholarPubMed
28.Odaka, Y, Nakano, M, Tanaka, T, et al. The influence of a high-fat dietary environment in the fetal period on postnatal metabolic and immune function. Obesity (Silver Spring). 2010; 18, 1688–1694.Google Scholar
29.Bourlier, V, Bouloumie, A. Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab. 2009; 35, 251–260.Google Scholar
30.de Luca, C, Olefsky, JM. Inflammation and insulin resistance. FEBS Lett. 2008; 582, 97–105.Google Scholar
31.Catalano, PM, Presley, L, Minium, J, Hauguel-de Mouzon, S. Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care. 2009; 32, 1076–1080.Google Scholar
32.Grayson, BE, Levasseur, PR, Williams, SM, et al. Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology. 2010; 151, 1622–1632.Google Scholar
33.Urbanek, M, Hayes, MG, Lee, H, et al. The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy. PLoS One. 2012; 7, e32958.Google Scholar
34.Dahlgren, J, Samuelsson, AM, Jansson, T, Holmang, A. Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation. Pediatr Res. 2006; 60, 147–151.Google Scholar
35.Lager, S, Asterholm, IW, Schele, E, et al. Perinatal lack of maternal IL-6 promotes increased adiposity during adulthood in mice. Endocrinology. 2011; 152, 1336–1346.Google Scholar
36.Zhu, MJ, Ma, Y, Long, NM, Du, M, Ford, SP. Maternal obesity markedly increases placental fatty acid transporter expression and fetal blood triglycerides at midgestation in the ewe. Am J Physiol Regul Integr Comp Physiol. 2010; 299, R1224–R1231.Google Scholar
37.Howie, GJ, Sloboda, DM, Kamal, T, Vickers, MH. Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol. 2009; 587(Pt 4), 905–915.Google Scholar
38.Jones, HN, Woollett, LA, Barbour, N, et al. High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice. Faseb J. 2009; 23, 271–278.Google Scholar
39.Zambrano, E, Martinez-Samayoa, PM, Rodriguez-Gonzalez, GL, Nathanielsz, PW. Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats. J Physiol. 2010; 588(Pt 10), 1791–1799.Google Scholar
40.Hulsmans, M, Van Dooren, E, Mathieu, C, Holvoet, P. Decrease of miR-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin. PLoS One. 2012; 7, e32794.Google Scholar
41.Mantzoros, CS, Li, T, Manson, JE, Meigs, JB, Hu, FB. Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes. J Clin Endocrinol Metab. 2005; 90, 4542–4548.Google Scholar
42.Bokarewa, M, Nagaev, I, Dahlberg, L, Smith, U, Tarkowski, A. Resistin, an adipokine with potent proinflammatory properties. J Immunol. 2005; 174, 5789–5795.Google Scholar
43.Rajala, MW, Qi, Y, Patel, HR, et al. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes. 2004; 53, 1671–1679.Google Scholar
44.Steppan, CM, Bailey, ST, Bhat, S, et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409, 307–312.Google Scholar
45.Heilbronn, LK, Rood, J, Janderova, L, et al. Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects. J Clin Endocrinol Metab. 2004; 89, 1844–1848.Google Scholar
46.Savage, DB, Sewter, CP, Klenk, ES, et al. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001; 50, 2199–2202.Google Scholar
47.Way, JM, Gorgun, CZ, Tong, Q, et al. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem. 2001; 276, 25651–25653.CrossRefGoogle ScholarPubMed
48.Caja, S, Martinez, I, Abelenda, M, Puerta, M. Resistin expression and plasma concentration peak at different times during pregnancy in rats. J Endocrinol. 2005; 185, 551–559.Google Scholar
49.Megia, A, Vendrell, J, Gutierrez, C, et al. Insulin sensitivity and resistin levels in gestational diabetes mellitus and after parturition. Eur J Endocrinol. 2008; 158, 173–178.Google Scholar
50.Nanda, S, Poon, LC, Muhaisen, M, Acosta, IC, Nicolaides, KH. Maternal serum resistin at 11 to 13 weeks’ gestation in normal and pathological pregnancies. Metabolism. 2012; 61, 699–705.Google Scholar
51.Cho, GJ, Yoo, SW, Hong, SC, et al. Correlations between umbilical and maternal serum resistin levels and neonatal birth weight. Acta Obstet Gynecol Scand. 2006; 85, 1051–1056.Google Scholar
52.Savino, F, Liguori, SA, Fissore, MF, Oggero, R. Breast milk hormones and their protective effect on obesity. Int J Pediatr Endocrinol. 2009; 2009, 327505.Google Scholar
53.Chan, TF, Tsai, YC, Wu, CH, et al. The positive correlation between cord serum retinol-binding protein 4 concentrations and fetal growth. Gynecol Obstet Invest. 2011; 72, 98–102.Google Scholar
54.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
55.Yang, Q, Graham, TE, Mody, N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005; 436, 356–362.CrossRefGoogle ScholarPubMed
56.Esposito, K, Pontillo, A, Giugliano, F, et al. Association of low interleukin-10 levels with the metabolic syndrome in obese women. J Clin Endocrinol Metab. 2003; 88, 1055–1058.Google Scholar
57.Juge-Aubry, CE, Somm, E, Pernin, A, et al. Adipose tissue is a regulated source of interleukin-10. Cytokine. 2005; 29, 270–274.Google Scholar
58.Renaud, SJ, Macdonald-Goodfellow, SK, Graham, CH. Coordinated regulation of human trophoblast invasiveness by macrophages and interleukin 10. Biol Reprod. 2007; 76, 448–454.Google Scholar
59.Bugatto, F, Fernandez-Deudero, A, Bailen, A, et al. Second-trimester amniotic fluid proinflammatory cytokine levels in normal and overweight women. Obstet Gynecol. 2010; 115, 127–133.Google Scholar
60.Ramsay, JE, Ferrell, WR, Crawford, L, et al. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab. 2002; 87, 4231–4237.Google Scholar
61.White, CL, Purpera, MN, Morrison, CD. Maternal obesity is necessary for programming effect of high-fat diet on offspring. Am J Physiol Regul Integr Comp Physiol. 2009; 296, R1464–R1472.Google Scholar
62.Farah, N, Hogan, AE, O'Connor, N, et al. Correlation between maternal inflammatory markers and fetomaternal adiposity. Cytokine. 2012; 60, 96–99.Google Scholar