Early Life Stress, Brain Development, and Obesity Risk: Is Oxytocin the Missing Link?

Abstract

Obesity disease results from a dysfunctional modulation of the energy balance whose master regulator is the central nervous system. The neural circuitries involved in such function complete their maturation during early postnatal periods, when the brain is highly plastic and profoundly influenced by the environment. This phenomenon is considered as an evolutionary strategy, whereby metabolic functions are adjusted to environmental cues, such as food availability and maternal care. In this timeframe, adverse stimuli may program the body metabolism to maximize energy storage abilities to cope with hostile conditions. Consistently, the prevalence of obesity is higher among individuals who experienced early life stress (ELS). Oxytocin, a hypothalamic neurohormone, regulates the energy balance and modulates social, emotional, and eating behaviors, exerting both central and peripheral actions. Oxytocin closely cooperates with leptin in regulating energy homeostasis. Both oxytocin and leptin impact the neurodevelopment during critical periods and are affected by ELS and obesity. In this review article, we report evidence from the literature describing the effect of postnatal ELS (specifically, disorganized/inconstant maternal care) on the vulnerability to obesity with a focus on the role of oxytocin. We emphasize the existing research gaps and highlight promising directions worthy of exploration. Based on the available data, alterations in the oxytocin system may in part mediate the ELS-induced susceptibility to obesity.

Early life stress and body-mass-index modulate brain connectivity in alcohol use disorder

“…Interestingly, we identified a negative association of the interaction effect of ELS events and BMI measures with the functional connectivity of SN seeds ACC with decision-making (MFG, precentral gyrus), RAIns and RSMG with visuo-motor control regions (LOC and supplementary motor cortex). Both pre-clinical and clinical studies have identified the contribution of ELS in increasing the risk for obesity [ 57 – 59 ] and AUD [ 48 , 60 , 61 ], which was attributed to persistent overactivation of the hypothalamic-pituitary-adrenal (HPA) axis [ 62 ], dysregulation of the mesolimbic dopamine functions [ 63 , 64 ] and an imbalance in connectivity patterns of salience, emotion and somatosensory networks [ 65 ]. Nonetheless, none of these studies demonstrated the combined relationship of increased occurrence of ELS events and BMI measures on brain connectivity in adults with AUD compared to those without AUD.…”

Early Life Stress and Body-Mass Index Modulate Brain Connectivity in Alcohol Use Disorder

“…On the other hand, a negative correlation was detected between the BMI levels of individuals with AUD and the connectivity of the right SMG with clusters in frontal regions that govern impulsive or self-control behaviors. Both pre-clinical and clinical studies have identified the contribution of ELS in increasing the risk for obesity 55 – 57 and AUD 32 , 58 , 59 , which was attributed to persistent overactivation of the hypothalamic-pituitary-adrenal (HPA) axis 60 , dysregulation of the mesolimbic dopamine functions 61 , 62 and an imbalance in connectivity patterns of salience, emotion and somatosensory networks 63 . Nonetheless, none of these studies demonstrated the relationship between ELS-influenced brain connectivity in adults with a comorbid occurrence of AUD and elevated BMI.…”

The Role of Oxytocin in Early-Life-Stress-Related Neuropsychiatric Disorders

“…Therefore, it is essential to understand the mechanisms by which ELS contributes to a variety of neuropsychiatric diseases in order to improve human health. In early life, the developing brain is extremely plastic, and neural circuit development during this period is influenced by life experiences, particularly negative stimuli [ 8 ]. The stress response comprises a series of neural events in the hypothalamus–pituitary–adrenal (HPA) axis that trigger a neuroendocrine cascade when activated.…”