Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

Abstract

The widespread consumption of ‘western’-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome.

Maternal body mass index in pregnancy and mental disorders in adult offspring: a record linkage study in Aberdeen, Scotland

“…These observations chime with the Developmental Origins of Health and Disease—framework of chronic illnesses, according to which prenatal adversity leads to permanent changes in the development of organs, cells, and body’s biological feedback mechanisms, thereby contributing to an increased risk of chronic illnesses, including mental disorders subsequently 38 . Supporting the DOHaD framework and the possible role of under-or overnutrition underlying our findings, previous studies have shown that maternal undernutrition during pregnancy due to famine exposure may predict the risks of several different mental disorders in the offspring 3 , 26 , 27 , 29 , that specific maternal dietary patterns may predict increased risks of psychiatric symptoms and suboptimal neurodevelopment in children 25 , and that maternal obesity, dietary patterns and undernutrition in pregnancy may each predict altered brain structure in the offspring 3 , 25 , 39 .…”

“…Neurobiologically, inflammatory pathways and other mechanisms related to individual’s altered stress vulnerability because of maternal obesity or underweight may have contributed to our findings. Obesity in pregnancy is a highly proinflammatory state 4 , 17 , 25 , 51 , and prenatal inflammation has been associated with psychopathology risk in the offspring 17 , 52 , 53 . Maternal BMI in pregnancy has been associated with altered functioning of the hypothalamus-pituitary adrenal axis in the offspring 54 , and changes in the functioning of this axis are characteristic of patients with mental disorders 55 .…”

“…Previous studies have shown that maternal overweight and obesity in pregnancy may also be associated with an increased risk of mental disorders and their symptoms in children 4 , 13 – 25 . A meta-analysis showed that maternal overweight (BMI 25–29.99 kg/m 2 ) and obesity predicted increased risks of attention deficit hyperactivity disorder, autism spectrum disorder, and developmental delay in children 14 .…”

Male Rat Offspring Are More Impacted by Maternal Obesity Induced by Cafeteria Diet than Females—Additive Effect of Postweaning Diet

“…While meta-analytic evidence suggests that obesogenic diets increase anxiety-like behaviour in the EPM and OFT in rodents consuming such a diet [60], here, we found anxiolytic effects of maternal Caf diet exposure in young offspring, regardless of whether these offspring were themselves fed a chow or Caf diet. Altered maternal care by Caf dams, maternal obesity-induced changes to offspring brain development, inflammatory changes, and maternal transfer of gut microbiota are among the mechanisms that may mediate behavioural changes in offspring [20,24].…”

“…Emerging evidence suggests that maternal obesity may also confer risk of behavioural changes in offspring [24]. A meta-analysis found that children of mothers with obesity, relative to those of normal weight, had 60% higher rates of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) [25].…”