Skip to main content Accessibility help

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

  • M. A. Kępczyńska (a1), E. T. Wargent (a1), M. A. Cawthorne (a1), J. R. S. Arch (a1), J. F. O'Dowd (a1) and C. J. Stocker (a1)...


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.


Corresponding author

*Address for correspondence: C. Stocker, Clore Laboratory, University of Buckingham, Hunter Street, Buckingham MK18 1EG, UK. (Email


Hide All
1.Franks, PW, Hanson, RL, Knowler, WC, et al. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med. 2010; 362, 485493.
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, 869873.
3.Catalano, PM, Farrell, K, Thomas, A, et al. Perinatal risk factors for childhood obesity and metabolic dysregulation. Am J Clin Nutr. 2009; 90, 13031313.
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, 15601567.
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, 11151121.
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, 7381.
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, 18721876.
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, 53655369.
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, 418424.
10.Nelson, SM, Matthews, P, Poston, L. Maternal metabolism and obesity: modifiable determinants of pregnancy outcome. Hum Reprod Update. 2010; 16, 255275.
11.Dabelea, D. The predisposition to obesity and diabetes in offspring of diabetic mothers. Diabetes Care. 2007; 30(Suppl 2), S169S174.
12.Hillier, TA, Pedula, KL, Schmidt, MM, et al. Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. Diabetes Care. 2007; 30, 22872292.
13.Hyperglycemia and Adverse Pregnancy Outcome (HAPO). Study: associations with neonatal anthropometrics. Diabetes. 2009; 58, 453459.
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, 611617.
15.Herrera, E, Amusquivar, E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000; 16, 202210.
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, 340346.
17.Stocker, CJ, Cawthorne, MA. The influence of leptin on early life programming of obesity. Trends Biotechnol. 2008; 26, 545551.
18.Briana, DD, Malamitsi-Puchner, A. The role of adipocytokines in fetal growth. Ann N Y Acad Sci. 2010; 1205, 8287.
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, R711R722.
20.Poston, L. Developmental programming and diabetes – the human experience and insight from animal models. Best Pract Res Clin Endocrinol Metab. 2010; 24, 541552.
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, 32193230.
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, 11331142.
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, 383392.
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, 451456.
25.Farley, D, Tejero, ME, Comuzzie, AG, et al. Feto-placental adaptations to maternal obesity in the baboon. Placenta. 2009; 30, 752760.
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.
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, 323335.
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, 16881694.
29.Bourlier, V, Bouloumie, A. Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab. 2009; 35, 251260. Luca, C, Olefsky, JM. Inflammation and insulin resistance. FEBS Lett. 2008; 582, 97105.
31.Catalano, PM, Presley, L, Minium, J, Hauguel-de Mouzon, S. Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care. 2009; 32, 10761080.
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, 16221632.
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.
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, 147151.
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, 13361346.
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, R1224R1231.
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), 905915.
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, 271278.
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), 17911799.
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.
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, 45424548.
42.Bokarewa, M, Nagaev, I, Dahlberg, L, Smith, U, Tarkowski, A. Resistin, an adipokine with potent proinflammatory properties. J Immunol. 2005; 174, 57895795.
43.Rajala, MW, Qi, Y, Patel, HR, et al. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes. 2004; 53, 16711679.
44.Steppan, CM, Bailey, ST, Bhat, S, et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409, 307312.
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, 18441848.
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, 21992202.
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, 2565125653.
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, 551559.
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, 173178.
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, 699705.
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, 10511056.
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.
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, 98102.
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, 146149.
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, 356362.
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, 10551058.
57.Juge-Aubry, CE, Somm, E, Pernin, A, et al. Adipose tissue is a regulated source of interleukin-10. Cytokine. 2005; 29, 270274.
58.Renaud, SJ, Macdonald-Goodfellow, SK, Graham, CH. Coordinated regulation of human trophoblast invasiveness by macrophages and interleukin 10. Biol Reprod. 2007; 76, 448454.
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, 127133.
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, 42314237.
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, R1464R1472.
62.Farah, N, Hogan, AE, O'Connor, N, et al. Correlation between maternal inflammatory markers and fetomaternal adiposity. Cytokine. 2012; 60, 9699.


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

  • M. A. Kępczyńska (a1), E. T. Wargent (a1), M. A. Cawthorne (a1), J. R. S. Arch (a1), J. F. O'Dowd (a1) and C. J. Stocker (a1)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed