The Influence of Obesity and Associated Fatty Acids on Placental Inflammation

Abstract

Purpose: Maternal obesity, affecting nearly 1 in 4 pregnancies, is associated with increased circulating saturated fatty acids, such as palmitate. These fatty acids are implicated in placental inflammation, which may in turn exacerbate both maternalefetal tolerance and responses to pathogens, such as group B Streptococcus. In this review, we address the question, "How do obesity and associated fatty acids influence placental inflammation?" Methods: In this narrative review, we searched PubMed and Google Scholar using combinations of the key words placental inflammation or pregnancy and lipids, fatty acids, obesity, palmitate, or other closely related search terms. We also used references found within these articles that may have been absent from our original search queries. We analyzed methods and key results of these articles to compare and contrast their findings, which were occasionally at odds with each other.Findings: Although obesity can be studied as a whole, complex phenomena with in vivo mouse models and human samples from patients with obesity, in vitro modeling often relies on the treatment of cells or tissues with 1 fatty acids and occasionally other compounds (eg, glucose and insulin). We found that palmitate, most commonly used in vitro to recreate hallmarks of obesity, induces apoptosis, oxidative stress, mitochondrial dysfunction, autophagy defects, and inflammasome activation in many placental cell types. We compare this to in vivo models of obesity wherever possible.We found that obesity as a whole may have more complex regulation of these phenomena (apoptosis, oxidative stress, mitochondrial dysfunction, autophagy defects, and inflammasome activation) compared with in vitro models of fatty acid treatment (primarily palmitate) because of the presence of unsaturated fatty acids (ie, oleate), which may have anti-inflammatory effects.Implications: The interaction of unsaturated fatty acids with saturated fatty acids may ameliorate many inflammatory effects of saturated fatty acids alone, which complicates interpretation of in vitro studies that focus on a particular fatty acid in isolation. This complication may explain why certain studies of obesity in vivo have differing outcomes from studies of specific fatty acids in vitro. (Clin Ther.

Maternal Pre-Pregnancy Body Mass Index, Gestational Weight Gain and Children’s Cognitive Development: A Birth Cohort Study

“…The Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study indicated that persistently high levels of maternal inflammation during pregnancy increased the risk of neurodevelopmental delay in children in cognitive, motor and social areas, and children of mothers with the highest levels of inflammation had the largest number of neurodevelopmental delay areas [ 35 ]. Maternal prepregnancy obesity or excessive weight gain during pregnancy would lead to chronic systemic inflammation and placental inflammatory response, causing increased concentrations of pro-inflammatory cytokines such as IL-6, IL-8, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) [ 36 , 37 ]. Exposure to an inflammatory environment in early life affects the development and function of fetal microglia, which are related to essential neurodevelopmental functions such as neuronal proliferation and differentiation, synapse formation, myelin formation and establishment of connections [ 38 ].…”

Maternal obesity: new placental paradigms unfolded

“…Although levels of both the saturated fatty acid palmitate and the monounsaturated fatty acid oleate are elevated in obese pregnant women [113], only exposure to palmitate facilitated the development of ER stress in the syncytiotrophoblast, driving translocation of ATF4 and downstream apoptosis mediated by C/EBP homologous protein (CHOP). Furthermore, increased placental palmitate content drives a potent inflammatory response in the obese placenta, including activation of the inflammasome and secretion of inflammatory cytokines [62,114]. This inflammatory response is likely to form a reciprocal cause-and-effect relationship with placental ER stress [91,104,115,116].…”

Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

“…Palmitic acid (PA, 16:0) and oleic acid (OA, 18:1) constitute 60% of fatty acids in lipids present in the maternal plasma by the end of pregnancy, and in both placenta and the fetus, these fatty acids act as fuel and as building blocks for the synthesis of structural and signaling lipids [ 6 , 7 , 8 ]. Both PA and OA are derived from diet and endogenous synthesis; thus, the fetus relies on both transplacental transfer and endogenous fetal–placental synthesis [ 9 ].…”

“…Excess PA is often negatively depicted for its potential involvement in the pathophysiology of adult chronic diseases such as cardiovascular disorders and diabetes, and excess intracellular un-esterified PA may induce lipotoxic effects [ 7 , 8 ], including in the placenta [ 10 ]. However, PA is also an essential fuel source, is a constituent of many signaling lipid molecules, is needed for the regulation of enzymatic activity though palmitoylation [ 7 ], and is involved in the production of pro-inflammatory cytokines [ 11 ], which are important in regulating pregnancy health and parturition.…”

“…However, PA is also an essential fuel source, is a constituent of many signaling lipid molecules, is needed for the regulation of enzymatic activity though palmitoylation [ 7 ], and is involved in the production of pro-inflammatory cytokines [ 11 ], which are important in regulating pregnancy health and parturition. Conversely, OA is often positively depicted, showing no pro-inflammatory effects and appearing to counter many damaging effects of excess PA [ 8 , 11 , 12 ]. For example, OA appears to protect trophoblasts from palmitate-induced death in vitro, possibly by inducing PA to be safely compartmentalized within lipid droplets [ 10 , 13 , 14 ].…”