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The impact of maternal obesity on inflammatory processes and consequences for later offspring health outcomes

Part of: DOHaD ANZ Conference 2016

Published online by Cambridge University Press:  27 March 2017

S. A. Segovia Open the ORCID record for S. A. Segovia [Opens in a new window] ,
M. H. Vickers  and
C. M. Reynolds
S. A. Segovia*
Affiliation:
Liggins Institute, University of Auckland, Auckland, New Zealand
M. H. Vickers
Affiliation:
Liggins Institute, University of Auckland, Auckland, New Zealand
C. M. Reynolds
Affiliation:
Liggins Institute, University of Auckland, Auckland, New Zealand
*
*Address for correspondence: C.M. Reynolds, Liggins Institute, The University of Auckland, Auckland 1023, New Zealand. (Email c.reynolds@auckland.ac.nz)
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Abstract

Obesity is a global epidemic, affecting both developed and developing countries. The related metabolic consequences that arise from being overweight or obese are a paramount global health concern, and represent a significant burden on healthcare systems. Furthermore, being overweight or obese during pregnancy increases the risk of offspring developing obesity and other related metabolic complications in later life, which can therefore perpetuate a transgenerational cycle of obesity. Obesity is associated with a chronic state of low-grade metabolic inflammation. However, the role of maternal obesity-mediated alterations in inflammatory processes as a mechanism underpinning developmental programming in offspring is less understood. Further, the use of anti-inflammatory agents as an intervention strategy to ameliorate or reverse the impact of adverse developmental programming in the setting of maternal obesity has not been well studied. This review will discuss the impact of maternal obesity on key inflammatory pathways, impact on pregnancy and offspring outcomes, potential mechanisms and avenues for intervention.

Keywords

developmental programminginflammationinterventionsmaternal obesity
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 5: Themed Issue: Australian Perspectives: Outcomes from the 2016 ANZ , October 2017 , pp. 529 - 540
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© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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References

1. Ng, M, Fleming, T, Robinson, M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384, 766–781.Google Scholar
2. Hossain, P, Kawar, B, El Nahas, M. Obesity and diabetes in the developing world – a growing challenge. N Engl J Med. 2007; 356, 213–215.CrossRefGoogle ScholarPubMed
3. Cordain, L, Eaton, SB, Sebastian, A, et al. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr. 2005; 81, 341–354.CrossRefGoogle Scholar
4. Mokdad, AH, Ford, ES, Bowman, BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003; 289, 76–79.CrossRefGoogle ScholarPubMed
5. Wilson, RM, Messaoudi, I. The impact of maternal obesity during pregnancy on offspring immunity. Mol Cell Endocrinol. 2015; 418, 134–142.CrossRefGoogle ScholarPubMed
6. Sebire, NJ, Jolly, M, Harris, J, et al. Maternal obesity and pregnancy outcome: a study of 287 213 pregnancies in London. Int J Obes (Lond). 2001; 25, 1175–1182.CrossRefGoogle Scholar
7. Catalano, PM, Ehrenberg, HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG. 2006; 113, 1126–1133.Google Scholar
8. Whitaker, RC. Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics. 2004; 114, e29–e36.CrossRefGoogle ScholarPubMed
9. Boney, CM, Verma, A, Tucker, R, et al. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005; 115, e290–e296.Google Scholar
10. Yu, Z, Han, S, Zhu, J, et al. Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PLoS One. 2013; 8, e61627.CrossRefGoogle ScholarPubMed
11. Vickers, M. Developmental programming and transgenerational transmission of obesity. Ann Nutr Metab. 2014; 64, 26–34.Google Scholar
12. O’Reilly, JR, Reynolds, RM. The risk of maternal obesity to the long‐term health of the offspring. Clin Endocrinol (Oxf). 2013; 78, 9–16.CrossRefGoogle Scholar
13. King, JC. Maternal obesity, metabolism, and pregnancy outcomes. Annu Rev Nutr. 2006; 26, 271–291.Google Scholar
14. Ramsay, JE, Ferrell, WR, Crawford, L, et al. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocr Metab. 2002; 87, 4231–4237.CrossRefGoogle ScholarPubMed
15. Lumeng, CN, Saltiel, AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011; 121, 2111–2117.Google Scholar
16. Kershaw, EE, Flier, JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004; 89, 2548–2556.Google Scholar
17. Lumeng, CN, Bodzin, JL, Saltiel, AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007; 117, 175–184.Google Scholar
18. Drolet, R, Bélanger, C, Fortier, M, et al. Fat depot‐specific impact of visceral obesity on adipocyte adiponectin release in women. Obesity. 2009; 17, 424–430.Google Scholar
19. Kim, JK, Gavrilova, O, Chen, Y, et al. Mechanism of insulin resistance in A-ZIP/F-1 fatless mice. J Biol Chem. 2000; 275, 8456–8460.Google Scholar
20. Ye, J, Gao, Z, Yin, J, et al. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007; 293, E1118–E1128.CrossRefGoogle Scholar
21. 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
22. Fain, JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006; 74, 443–477.Google Scholar
23. Silha, JV, Krsek, M, Skrha, JV, et al. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol. 2003; 149, 331–335.Google Scholar
24. Cnop, M, Havel, P, Utzschneider, K, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia. 2003; 46, 459–469.Google Scholar
25. Wildman, RP, Muntner, P, Reynolds, K, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). Arch Intern Med. 2008; 168, 1617–1624.CrossRefGoogle ScholarPubMed
26. Mongraw-Chaffin, M, Foster, MC, Kalyani, RR, et al. Obesity severity and duration are associated with incident metabolic syndrome: evidence against metabolically healthy obesity from the multi-ethnic study of atherosclerosis. J Clin Endocrinol Metab. 2016; 101, 4117–4124.Google Scholar
27. Hinnouho, GM, Czernichow, S, Dugravot, A, et al. Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care. 2013; 36, 2294–2300.Google Scholar
28. Hotamisligil, GS, Shargill, NS, Spiegelman, BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993; 259, 87–91.CrossRefGoogle ScholarPubMed
29. Hotamisligil, GS, Arner, P, Caro, JF, et al. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995; 95, 2409–2415.CrossRefGoogle ScholarPubMed
30. Chen, X, Xun, K, Chen, L, et al. TNF‐α, a potent lipid metabolism regulator. Cell Biochem Funct. 2009; 27, 407–416.Google Scholar
31. Uysal, KT, Wiesbrock, SM, Marino, MW, et al. Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature. 1997; 389, 610–614.CrossRefGoogle ScholarPubMed
32. Lagathu, C, Yvan-Charvet, L, Bastard, J, et al. Long-term treatment with interleukin-1β induces insulin resistance in murine and human adipocytes. Diabetologia. 2006; 49, 2162–2173.Google Scholar
33. McGillicuddy, FC, Harford, KA, Reynolds, CM, et al. Lack of interleukin-1 receptor I (IL-1RI) protects mice from high-fat diet-induced adipose tissue inflammation coincident with improved glucose homeostasis. Diabetes. 2011; 60, 1688–1698.Google Scholar
34. Kim, J, Bachmann, RA, Chen, J. Interleukin‐6 and insulin resistance. Vitam Horm. 2009; 80, 613–633.CrossRefGoogle ScholarPubMed
35. Mohamed-Ali, V, Goodrick, S, Rawesh, A, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-α, in vivo 1. J Clin Endocrinol Metab. 1997; 82, 4196–4200.Google ScholarPubMed
36. Rotter, V, Nagaev, I, Smith, U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem. 2003; 278, 45777–45784.Google Scholar
37. Senn, JJ, Klover, PJ, Nowak, IA, et al. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes. 2002; 51, 3391–3399.Google Scholar
38. Pedersen, BK, Steensberg, A, Schjerling, P. Muscle‐derived interleukin‐6: possible biological effects. J Physiol (Lond). 2001; 536, 329–337.CrossRefGoogle ScholarPubMed
39. Hu, FB, Meigs, JB, Li, TY, et al. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004; 53, 693–700.CrossRefGoogle ScholarPubMed
40. Kopp, HP, Kopp, CW, Festa, A, et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003; 23, 1042–1047.Google Scholar
41. Matthews, V, Allen, T, Risis, S, et al. Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia. 2010; 53, 2431–2441.Google Scholar
42. van Exel, E, Gussekloo, J, de Craen, AJ, et al. Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes : the Leiden 85-Plus Study. Diabetes. 2002; 51, 1088–1092.Google Scholar
43. Fiorentino, DF, Zlotnik, A, Mosmann, TR, et al. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991; 147, 3815–3822.Google Scholar
44. Belo, L, Santos-Silva, A, Rocha, S, et al. Fluctuations in C-reactive protein concentration and neutrophil activation during normal human pregnancy. Eur J Obstet Gynecol Reprod Biol. 2005; 123, 46–51.CrossRefGoogle ScholarPubMed
45. Zhang, L, Sugiyama, T, Murabayashi, N, et al. The inflammatory changes of adipose tissue in late pregnant mice. J Mol Endocrinol. 2011; 47, 157–165.Google Scholar
46. Madan, JC, Davis, JM, Craig, WY, et al. Maternal obesity and markers of inflammation in pregnancy. Cytokine. 2009; 47, 61–64.Google Scholar
47. Retnakaran, R, Hanley, AJ, Raif, N, et al. C-reactive protein and gestational diabetes: the central role of maternal obesity. J Clin Endocrinol Metab. 2003; 88, 3507–3512.CrossRefGoogle ScholarPubMed
48. Basu, S, Haghiac, M, Surace, P, et al. Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity. 2011; 19, 476–482.Google Scholar
49. Kalagiri, RR, Carder, T, Choudhury, S, et al. Inflammation in complicated pregnancy and its outcome. Am J Perinatol. 2016; 14, 1337–1356.Google Scholar
50. Arenz, S, Rückerl, R, Koletzko, B, et al. Breast-feeding and childhood obesity – a systematic review. Int J Obes. 2004; 28, 1247–1256.CrossRefGoogle ScholarPubMed
51. Panagos, P, Vishwanathan, R, Penfield-Cyr, A, et al. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol. 2016; 36, 284–290.CrossRefGoogle ScholarPubMed
52. Morigny, P, Houssier, M, Mouisel, E, et al. Adipocyte lipolysis and insulin resistance. Biochimie. 2016; 125, 259–266.CrossRefGoogle ScholarPubMed
53. Zambrano, E, Nathanielsz, PW. Mechanisms by which maternal obesity programs offspring for obesity: evidence from animal studies. Nutr Rev. 2013; 71(Suppl. 1), S42–S54.Google Scholar
54. Tschop, M, Weyer, C, Tataranni, PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001; 50, 707–709.CrossRefGoogle ScholarPubMed
55. Collden, G, Balland, E, Parkash, J, et al. Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin. Mol Metab. 2015; 4, 15–24.Google Scholar
56. Huh, SY, Rifas-Shiman, SL, Taveras, EM, et al. Timing of solid food introduction and risk of obesity in preschool-aged children. Pediatrics. 2011; 127, e544–e551.CrossRefGoogle ScholarPubMed
57. Radaelli, T, Uvena-Celebrezze, J, Minium, J, et al. Maternal interleukin-6: marker of fetal growth and adiposity. J Soc Gynecol Investig. 2006; 13, 53–57.CrossRefGoogle ScholarPubMed
58. McCloskey, K, Ponsonby, A, Collier, F, et al.The association between higher maternal pre‐pregnancy body mass index and increased birth weight, adiposity and inflammation in the newborn. Pediatr Obes. 2016. https://doi.org/10.1111/ijpo.12187.CrossRefGoogle Scholar
59. Gaillard, R, Rifas‐Shiman, SL, Perng, W, et al. Maternal inflammation during pregnancy and childhood adiposity. Obesity. 2016; 24, 1320–1327.CrossRefGoogle ScholarPubMed
60. Farah, N, Hogan, AE, O’Connor, N, et al. Correlation between maternal inflammatory markers and fetomaternal adiposity. Cytokine. 2012; 60, 96–99.CrossRefGoogle ScholarPubMed
61. Toledo Baldi, E, Dias Bóbbo, V, Melo Lima, M, et al. Tumor necrosis factor‐alpha levels in blood cord is directly correlated with the body weight of mothers. Obes Sci Pract. 2016; 2, 210–214.Google Scholar
62. Danielsen, I, Granström, C, Rytter, D, et al. Subclinical inflammation during third trimester of pregnancy was not associated with markers of the metabolic syndrome in young adult offspring. Obesity. 2014; 22, 1351–1358.CrossRefGoogle Scholar
63. Onore, CE, Schwartzer, JJ, Careaga, M, et al. Maternal immune activation leads to activated inflammatory macrophages in offspring. Brain Behav Immun. 2014; 38, 220–226.Google Scholar
64. Kirsten, TB, Lippi, LL, Bevilacqua, E, et al. LPS exposure increases maternal corticosterone levels, causes placental injury and increases IL-1Beta levels in adult rat offspring: relevance to autism. PLoS One. 2013; 8, e82244.Google Scholar
65. Nilsson, C, Larsson, B, Jennische, E, et al. Maternal endotoxemia results in obesity and insulin resistance in adult male offspring 1. Endocrinology. 2001; 142, 2622–2630.Google Scholar
66. Murabayashi, N, Sugiyama, T, Zhang, L, et al. Maternal high-fat diets cause insulin resistance through inflammatory changes in fetal adipose tissue. Eur J Obstet Gyn R B. 2013; 169, 39–44.Google Scholar
67. Alfaradhi, MZ, Kusinski, LC, Fernandez-Twinn, DS, et al. Maternal obesity in pregnancy developmentally programs adipose tissue inflammation in young, lean male mice offspring. Endocrinology. 2016; 157, 4246–4256.Google Scholar
68. Challier, JC, Basu, S, Bintein, T, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta. 2008; 29, 274–281.Google Scholar
69. Zhu, MJ, Du, M, Nathanielsz, PW, et al. Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta. Placenta. 2010; 31, 387–391.Google Scholar
70. Halaas, JL, Gajiwala, KS, Maffei, M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995; 269, 543–546.Google Scholar
71. Loffreda, S, Yang, SQ, Lin, HZ, et al. Leptin regulates proinflammatory immune responses. FASEB J. 1998; 12, 57–65.Google Scholar
72. Lappas, M, Permezel, M, Rice, GE. Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-κB, peroxisomal proliferator-activated receptor-γ and extracellularly regulated kinase 1/2. Endocrinology. 2005; 146, 3334–3342.Google Scholar
73. Schwartz, MW, Peskind, E, Raskind, M, et al. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med. 1996; 2, 589–593.Google Scholar
74. Shankar, K, Harrell, A, Liu, XL, et al. Maternal obesity at conception programs obesity in the offspring. Am J Physiol-Reg I. 2008; 294, R528–R538.Google Scholar
75. Oben, JA, Mouralidarane, A, Samuelsson, AM, et al. Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice. J Hepatol. 2010; 52, 913–920.Google Scholar
76. Sáinz, N, González-Navarro, CJ, Martínez, JA, et al. Leptin signaling as a therapeutic target of obesity. Expert Opin Ther Targets. 2015; 19, 893–909.CrossRefGoogle ScholarPubMed
77. Lihn, AS, Bruun, JM, He, G, et al. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Mol Cell Endocrinol. 2004; 219, 9–15.CrossRefGoogle ScholarPubMed
78. Park, K, Park, KS, Kim, M, et al. Relationship between serum adiponectin and leptin concentrations and body fat distribution. Diabetes Res Clin Pract. 2004; 63, 135–142.CrossRefGoogle ScholarPubMed
79. Yamauchi, T, Kamon, J, Minokoshi, Ya, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002; 8, 1288–1295.Google Scholar
80. Ohashi, K, Parker, JL, Ouchi, N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2010; 285, 6153–6160.CrossRefGoogle ScholarPubMed
81. 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
82. Aye, IL, Rosario, FJ, Powell, TL, et al. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth. Proc Natl Acad Sci U S A. 2015; 112, 12858–12863.Google Scholar
83. Saben, J, Lindsey, F, Zhong, Y, et al. Maternal obesity is associated with a lipotoxic placental environment. Placenta. 2014; 35, 171–177.Google Scholar
84. Dosch, NC, Guslits, EF, Weber, MB, et al. Maternal obesity affects inflammatory and iron indices in umbilical cord blood. J Pediatr. 2016; 172, 20–28.Google Scholar
85. Kroener, L, Wang, ET, Pisarska, MD. Predisposing factors to abnormal first trimester placentation and the impact on fetal outcomes. Semin Reprod Med. 2016; 34, 27–35.Google Scholar
86. Hayes, EK, Tessier, DR, Percival, ME, et al. Trophoblast invasion and blood vessel remodeling are altered in a rat model of lifelong maternal obesity. Reprod Sci. 2014; 21, 648–657.Google Scholar
87. Lager, S, Jansson, N, Olsson, A, et al. Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells. Placenta. 2011; 32, 121–127.Google Scholar
88. Huang, L, Liu, J, Feng, L, et al. Maternal prepregnancy obesity is associated with higher risk of placental pathological lesions. Placenta. 2014; 35, 563–569.Google Scholar
89. Mark, P, Sisala, C, Connor, K, et al. A maternal high-fat diet in rat pregnancy reduces growth of the fetus and the placental junctional zone, but not placental labyrinth zone growth. J DOHaD. 2011; 2, 63–70.Google Scholar
90. Mark, P, Lewis, J, Jones, M, et al. The inflammatory state of the rat placenta increases in late gestation and is further enhanced by glucocorticoids in the labyrinth zone. Placenta. 2013; 34, 559–566.Google Scholar
91. Farley, D, Choi, J, Dudley, D, et al. Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity. Placenta. 2010; 31, 718–724.Google Scholar
92. Leon-Garcia, SM, Roeder, HA, Nelson, KK, et al. Maternal obesity and sex-specific differences in placental pathology. Placenta. 2016; 38, 33–40.Google Scholar
93. Ditchfield, A, Desforges, M, Mills, T, et al. Maternal obesity is associated with a reduction in placental taurine transporter activity. Int J Obes. 2014; 4, 557–564.Google Scholar
94. Dube, E, Gravel, A, Martin, C, et al. Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta. Biol Reprod. 2012; 87, 1–11.Google Scholar
95. Langley-Evans, SC. Developmental programming of health and disease. Proc Nutr Soc. 2006; 65, 97–105.CrossRefGoogle ScholarPubMed
96. Hanson, MA, Gluckman, PD. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev. 2014; 94, 1027–1076.Google Scholar
97. Petersen, AM, Pedersen, BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985). 2005; 98, 1154–1162.Google Scholar
98. Ford, ES. Does exercise reduce inflammation? Physical activity and C-reactive protein among US adults. Epidemiology. 2002; 13, 561–568.CrossRefGoogle Scholar
99. Vega, CC, Reyes-Castro, LA, Bautista, CJ, et al. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism. Int J Obes. 2013; 4, 712–719.Google Scholar
100. Bae-Gartz, I, Janoschek, R, Kloppe, CS, et al. Running exercise in obese pregnancies prevents IL-6 trans-signaling in male offspring. Med Sci Sports Exerc. 2016; 48, 829–838.Google Scholar
101. Tinius, RA, Cahill, AG, Strand, EA, et al. Maternal inflammation during late pregnancy is lower in physically active compared with inactive obese women. Appl Physiol Nutr Metab. 2015; 41, 191–198.Google Scholar
102. Chen, H, Simar, D, Pegg, K, et al. Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents. Diabetologia. 2014; 57, 614–622.Google Scholar
103. Heliövaara, M, Herz, M, Teppo, A, et al. Pioglitazone has anti-inflammatory effects in patients with type 2 diabetes. J Endocrinol Invest. 2007; 30, 292–297.Google Scholar
104. Kalanderian, A, Abate, N, Patrikeev, I, et al. Pioglitazone therapy in mouse offspring exposed to maternal obesity. Am J Obstet Gynecol. 2013; 208, 308 e1–7.Google Scholar
105. Desai, N, Roman, A, Rochelson, B, et al. Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome. Am J Obstet Gynecol. 2013; 209, 136.e1–9.Google Scholar
106. Harris, K, Desai, N, Gupta, M, et al. The effects of prenatal metformin on obesogenic diet-induced alterations in maternal and fetal fatty acid metabolism. Nutr Metab (Lond). 2016; 13, 55.Google Scholar
107. Salomäki, H, Heinäniemi, M, Vähätalo, LH, et al. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring. PLoS One. 2014; 9, e115778.Google Scholar
108. Chiswick, CA, Reynolds, RM, Denison, FC, et al. Efficacy of metformin in pregnant obese women: a randomised controlled trial. BMJ Open. 2015; 5, e006854.Google Scholar
109. Chiswick, C, Reynolds, RM, Denison, F, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2015; 3, 778–786.Google Scholar
110. Novak, TE, Babcock, TA, Jho, DH, et al. NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol. 2003; 284, L84–L89.Google Scholar
111. Neschen, S, Morino, K, Rossbacher, JC, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. 2006; 55, 924–928.Google Scholar
112. Haghiac, M, Yang, X, Presley, L, et al. Dietary omega-3 fatty acid supplementation reduces inflammation in obese pregnant women: a randomized double-blind controlled clinical trial. PLoS One. 2015; 10, e0137309.Google Scholar
113. Melody, S, Vincent, R, Mori, T, et al. Effects of omega-3 and omega-6 fatty acids on human placental cytokine production. Placenta. 2015; 36, 34–40.CrossRefGoogle ScholarPubMed
114. Moon, R, Harvey, N, Robinson, S, et al. Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood. J Clin Endocrinol Metab. 2012; 98, 299–307.Google Scholar
115. Rytter, D, Bech, BH, Halldorsson, T, et al. No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring. Br J Nutr. 2013; 110, 2037–2046.Google Scholar
116. Brei, C, Stecher, L, Much, D, et al. Reduction of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring body composition: follow-up results from a randomized controlled trial up to 5 y of age. Am J Clin Nutr. 2016; 103, 1472–1481.CrossRefGoogle ScholarPubMed
117. Stratakis, N, Gielen, M, Chatzi, L, et al. Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2014; 68, 1277–1287.Google Scholar
118. Simopoulos, AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002; 56, 365–379.Google Scholar
119. Simopoulos, AP. An increase in the omega-6/omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016; 8, 128.Google Scholar
120. Heerwagen, MJ, Stewart, MS, de la Houssaye, BA, et al. Transgenic increase in n-3/n-6 fatty acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice. PLoS One. 2013; 8, e67791.Google Scholar
121. Hussain, A, Nookaew, I, Khoomrung, S, et al. A maternal diet of fatty fish reduces body fat of offspring compared with a maternal diet of beef and a post‐weaning diet of fish improves insulin sensitivity and lipid profile in adult C57BL/6 male mice. Acta Physiol (Oxf). 2013; 209, 220–234.CrossRefGoogle Scholar
122. Bagley, HN, Wang, Y, Campbell, MS, et al. Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition. J Obes. 2013; 2013, 312153.Google Scholar
123. Muhlhausler, BS, Miljkovic, D, Fong, L, et al. Maternal omega-3 supplementation increases fat mass in male and female rat offspring. Front Genet. 2011; 2, 48.Google Scholar
124. Zulkafli, IS, Waddell, BJ, Mark, PJ. Postnatal dietary omega-3 fatty acid supplementation rescues glucocorticoid-programmed adiposity, hypertension, and hyperlipidemia in male rat offspring raised on a high-fat diet. Endocrinology. 2013; 154, 3110–3117.Google Scholar
125. Mark, PJ, Wyrwoll, CS, Zulkafli, IS, et al. Rescue of glucocorticoid-programmed adipocyte inflammation by omega-3 fatty acid supplementation in the rat. Reprod Biol Endocrinol. 2014; 12, 1.Google Scholar
126. Chicco, A, Creus, A, Illesca, P, et al. Effects of post-suckling n-3 polyunsaturated fatty acids: prevention of dyslipidemia and liver steatosis induced in rats by a sucrose-rich diet during pre-and post-natal life. Food Funct. 2016; 7, 445–454.Google Scholar
127. Balogun, KA, Cheema, SK. Dietary omega-3 fatty acids prevented adipocyte hypertrophy by downregulating DGAT-2 and FABP-4 in a sex-dependent fashion. Lipids. 2016; 51, 25–38.CrossRefGoogle Scholar
128. Muhlhausler, B, Gibson, R, Makrides, M. The effect of maternal omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during pregnancy and/or lactation on body fat mass in the offspring: a systematic review of animal studies. Prostaglandins Leukot Essent Fatty Acids. 2011; 85, 83–88.Google Scholar
129. Mennitti, LV, Oliveira, JL, Morais, CA, et al. Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring. J Nutr Biochem. 2015; 26, 99–111.Google Scholar
130. Kennedy, A, Martinez, K, Schmidt, S, et al. Antiobesity mechanisms of action of conjugated linoleic acid. J Nutr Biochem. 2010; 21, 171–179.Google Scholar
131. Bauman, D, Baumgard, L, Corl, B, et al. Biosynthesis of conjugated linoleic acid in ruminants. J Anim Sci. 2000; 77, 1–15.Google Scholar
132. Viladomiu, M, Hontecillas, R, Bassaganya-Riera, J. Modulation of inflammation and immunity by dietary conjugated linoleic acid. Eur J Pharmacol. 2015; 785, 87–95.Google Scholar
133. Dhiman, TR, Nam, S, Ure, AL. Factors affecting conjugated linoleic acid content in milk and meat. Crit Rev Food Sci Nutr. 2005; 45, 463–482.CrossRefGoogle ScholarPubMed
134. Banni, S. Conjugated linoleic acid metabolism. Curr Opin Lipidol. 2002; 13, 261–266.Google Scholar
135. West, DB, Delany, JP, Camet, PM, et al. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol. 1998; 275, R667–R672.Google Scholar
136. Houseknecht, KL, Heuvel, JPV, Moya-Camarena, SY, et al. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem Biophys Res Commun. 1998; 244, 678–682.Google Scholar
137. Kritchevsky, D, Tepper, SA, Wright, S, et al. Influence of graded levels of conjugated linoleic acid (CLA) on experimental atherosclerosis in rabbits. Nutr Res. 2002; 22, 1275–1279.Google Scholar
138. de Roos, B, Rucklidge, G, Reid, M, et al. Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach. FASEB J. 2005; 19, 1746–1748.Google Scholar
139. Jaudszus, A, Krokowski, M, Mockel, P, et al. Cis-9, trans-11-conjugated linoleic acid inhibits allergic sensitization and airway inflammation via a PPARgamma-related mechanism in mice. J Nutr. 2008; 138, 1336–1342.Google Scholar
140. Moloney, F, Toomey, S, Noone, E, et al. Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue. Diabetes. 2007; 56, 574–582.Google Scholar
141. Bassaganya-Riera, J, Reynolds, K, Martino-Catt, S, et al. Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology. 2004; 127, 777–791.Google Scholar
142. Belury, MA, Moya-Camarena, SY, Lu, M, et al. Conjugated linoleic acid is an activator and ligand for peroxisome proliferator-activated receptor-gamma (PPAR gamma). Nutr Res. 2002; 22, 817–824.Google Scholar
143. Cheng, W, Lii, C, Chen, H, et al. Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-κB pathway. J Agric Food Chem. 2004; 52, 71–78.Google Scholar
144. Reynolds, CM, Loscher, CE, Moloney, AP, et al. Cis-9, trans-11-conjugated linoleic acid but not its precursor trans-vaccenic acid attenuate inflammatory markers in the human colonic epithelial cell line Caco-2. Br J Nutr. 2008; 100, 13–17.Google Scholar
145. Reynolds, CM, Draper, E, Keogh, B, et al. A conjugated linoleic acid-enriched beef diet attenuates lipopolysaccharide-induced inflammation in mice in part through PPARgamma-mediated suppression of toll-like receptor 4. J Nutr. 2009; 139, 2351–2357.Google Scholar
146. Park, Y, Storkson, JM, Albright, KJ, et al. Evidence that the trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids. 1999; 34, 235–241.Google Scholar
147. Segovia, SA, Vickers, MH, Zhang, XD, et al. Maternal supplementation with conjugated linoleic acid in the setting of diet-induced obesity normalises the inflammatory phenotype in mothers and reverses metabolic dysfunction and impaired insulin sensitivity in offspring. J Nutr Biochem. 2015; 26, 1448–1457.Google Scholar