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

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.

Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications

“…Adipocytes hypertrophy disturbs the balance of adipose tissue-derived cytokines and adipokines, leading to a proinflammatory state with subsequent adipocytes cellular dysfunction, which inhibits adiponectin mRNA expression and stimulates endoplasmic reticulum stress [22]. This is also associated with increased secretion of proinflammatory cytokines and MCP-1, causing a typical infiltration of activated macrophages that further promotes the inflammatory process [23]. The level of circulating leptin concentration is elevated with the subsequent reduction in the concentration of adiponectin [24].…”

“…Adipocytes hypertrophy alters the balance of adipose tissue-derived cytokines, hemostasis, and adipokines, leading to proinflammatory and prothrombotic states [22]. These trigger the increased secretion of proinflammatory cytokines, prothrombotic markers, and a typical infiltration of endothelium by activated macrophages, further promoting inflammatory process [23]. Indeed, inflammation is associated with elevated levels of circulating inflammatory cytokines and prothrombotic markers observed in patients with obesity-related endothelial dysfunction [5].…”

Prepregnancy obesity is associated with lower psychomotor development scores in boys at age 3 in a low-income, minority birth cohort

“…The physiological mechanisms linking maternal adiposity, GWG, and early cognition are intricate and likely differ between boys and girls. Potential mechanisms associated with excess adiposity may produce an inimical prenatal environment including dysregulation of lipid, insulin, and appetite or increased estrogen and inflammatory signaling; 26,[68][69][70] specific dietary patterns, including high-fat diet, excess free fatty acids or glucose, or micronutrient deficiencies; 20,26,71 altered placental transport mechanisms; 68,70,72 a lipotoxic environment for brain development; 73,74 excessive production of reactive oxygen species and reduction in placental ATP generation; [75][76][77] or alterations in serotonergic and dopaminergic signaling pathways. 20 Fetal growth differs between sexes in rate and efficiency of the placental response to maternal adiposity; 38 boys grow faster, larger, require more placental efficiency to grow at this accelerated rate, 35,37,80 and male placentas are more vulnerable to placental inefficiency from inflammatory, oxidative, and nitrative stress from maternal adiposity.…”

Maternal Stress Potentiates the Effect of an Inflammatory Diet in Pregnancy on Maternal Concentrations of Tumor Necrosis Factor Alpha

“…Results of the current study suggest that higher levels of perceived stress are significantly associated with consumption of a diet with greater inflammatory potential, and that perceived stress potentiates the effects of a pro-inflammatory diet on TNF-α levels across pregnancy. Since increased adiposity is strongly associated with low-grade chronic inflammation in non-pregnant and pregnant populations [ 88 , 89 , 90 ], including a positive association with TNF-α [ 91 ], we also explored the relationship of maternal pre-pregnancy BMI status with the effects of DII and the DII*PSS interaction on TNF-α across pregnancy. The results were not altered by either including or excluding pre-pregnancy BMI as a covariate, suggesting that a pro-inflammatory diet alone—as well as in combination with maternal stress—influences levels of maternal TNF-α irrespective of BMI status.…”