Changes in PPAR-γ Expression Are Associated with microRNA Profiles during Fetal Programming due to Maternal Overweight and Obesity

Abstract

<b><i>Background:</i></b> There has been a global increase in the prevalence of obesity in pregnant women in recent years. Animal studies have shown that intrauterine environment associated with maternal obesity leads to epigenetic changes. However, the effects of epigenetic changes occurring before birth in response to maternal conditions have not been clearly characterized in humans. <b><i>Objective:</i></b> The aim of the study was to analyze peroxisome proliferator-activated receptor (PPAR)-γ expression in cell cultures from newborns from mothers with overweight and obesity, in response to in vitro metabolic challenges and their relationship with microRNA profile and cytokine expression. <b><i>Methods/Study design:</i></b> The profile of circulating microRNAs from 72 mother-child pairs (including healthy infants born to normal weight [<i>n</i> = 35], overweight [<i>n</i> = 25], and obese [<i>n</i> = 12] mothers) was determined through real-time PCR, and the PPAR-γ expression in peripheral blood mononuclear cell cultures from offspring was analyzed after in vitro challenges. <b><i>Results:</i></b> miR-146a, miR-155, and miR-378a were upregulated in overweight mothers, while miR-378a was upregulated in obese mothers compared to normal weight mothers. In children from overweight mothers, miR-155 and miR-221 were downregulated and miR-146a was upregulated, while offspring of mothers with obesity showed downregulation of miR-155, miR-221, and miR-1301. These microRNAs have direct or indirect relation with PPAR-γ expression. In vitro exposure to high triglyceride and exposure to miR-378a induced a higher expression of PPAR-γ in cells from offspring of mothers with overweight and obesity. In contrast, cells from offspring of mothers with obesity cultured with high glucose concentrations showed PPAR-γ downregulation. IL-1ß, IL-6, and TNF-α expression in cells of offspring of overweight and obese mothers differed from that of offspring of normal weight mothers. Limitation of our study is the small sample size. <b><i>Conclusion:</i></b> The blood microRNA profile, and in vitro PPAR-γ and inflammatory cytokine expression in cells of newborn infants are associated with maternal obesity indicating that epigenetic marks may be established during intrauterine development. <b><i>Key Message:</i></b> Neonatal microRNA profile is associated with maternal weight. Neonatal microRNA profile is independent of maternal microRNA profile. PPAR-γ expression in newborn cell cultures is affected by maternal weight

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“…The miRNA profile in mononuclear cells showed a downregulation of miR-155, miR-221, and miR-1301, as well as upregulation of miR-146a in the circulation of newborns from overweight and obese mothers. Moreover, the study showed that in the same samples from newborns, the RNA profile changes induced by overweight mothers and obesity were also associated to alteration in PPAR-γ gene expression, a master regulator of adipogenesis and altered cytokine pro-inflammatory levels in vitro blood mononuclear cell response to metabolic stimuli ( 142 ).…”