Maternal obesity and developmental programming of neuropsychiatric disorders: An inflammatory hypothesis

Abstract

Maternal obesity is associated with the development of a variety of neuropsychiatric disorders; however, the mechanisms behind this association are not fully understood. Comparison between maternal immune activation and maternal obesity reveals similarities in associated impairments and maternal cytokine profile. Here, we present a summary of recent evidence describing how inflammatory processes contribute towards the development of neuropsychiatric disorders in the offspring of obese mothers. This includes discussion on how maternal cytokine levels, fatty acids and placental inflammation may interact with foetal neurodevelopment through changes to microglial behaviour and epigenetic modification. We also propose an exosome-mediated mechanism for the disruption of brain development under maternal obesity and discuss potential intervention strategies.

Longitudinal phenotyping of maternal antenatal depression in obese pregnant women supports multiple-hit hypothesis for fetal brain development, a secondary analysis of the UPBEAT study

“… 28 The implication for the fetus lies in the known effects of maternal high-fat and high-sugar diets on neurodevelopment. 29 Although there was only a trend to higher absolute FA subtypes concentrations in the blood of the Severe class, there was evidence for a lower LDL/HDL and higher blood FA unsaturation in the Mild class. Additionally, lower dietary protein intake (% E) in the Severe and Moderate classes could suggest heterogeneity in serotonin precursor availability within the fetal brain, necessarily derived from maternal dietary protein.…”

Non-Linear and Sex-Specific Effect of Maternal Pre-Pregnancy BMI on Emotional and Behavioral Development of Preschool Children: A Population-Based Cohort Study

“…IL-6 and members of TGF and TNF families regulate many developmental processes from initial central nervous system (CNS) formation to synaptogenesis [ 35 ]. Dysregulation of these factors through maternal obesity may contribute to increased offspring’s susceptibility to neurodevelopmental disorders [ 36 ]. Animal experiments found increased circulating IL-6 and reduced innervation of the hypothalamic paraventricular nucleus in newborn mice of obese dams compared with those of dams with normal weight [ 37 ].…”

Inflammatory Signatures of Maternal Obesity as Risk Factors for Neurodevelopmental Disorders: Role of Maternal Microbiota and Nutritional Intervention Strategies

“…The chronic low-grade systemic inflammation characterizing maternal obesity is similar to that observed as a result of an early-life bacterial infection and suggests that common molecular and cellular mechanisms are activated by these different prenatal conditions [ 13 , 47 , 48 ]. The mechanisms mediating the propagation of maternal inflammation to the developing fetal brain are poorly elucidated, although the microenvironment generated by the placenta at the maternal/fetal interface is emerging as central in this phenomenon [ 13 , 49 ].…”

“…The chronic low-grade systemic inflammation characterizing maternal obesity is similar to that observed as a result of an early-life bacterial infection and suggests that common molecular and cellular mechanisms are activated by these different prenatal conditions [ 13 , 47 , 48 ]. The mechanisms mediating the propagation of maternal inflammation to the developing fetal brain are poorly elucidated, although the microenvironment generated by the placenta at the maternal/fetal interface is emerging as central in this phenomenon [ 13 , 49 ]. Altered ratios of innate and adaptive immune cell subsets and increased expression of placental pro-inflammatory and oxidative factors interfere with fetal development through several mechanisms, including maternal delivery of metabolites, nutrients, hormones, antibodies, and also cells, to the fetus [ 50 ].…”

“…Inflammation has recently obtained widespread attention as a likely mediating mechanism for its involvement in the pathophysiology of both obesity and mental disorders [ 13 ] and for the emerging role of inflammatory mediators as regulators of brain homeostasis and plasticity [ 14 , 15 , 16 ]. As a general mechanism, the expansion of adipose tissue observed in obese subjects is associated with increased size and number of adipocytes leading to adipocyte hypoxia, infiltration of leukocytes, inflammation and insulin resistance [ 17 , 18 , 19 ].…”