The impact of maternal high-fat diet consumption on neural development and behavior of offspring

Abstract

Maternal diet and metabolic state are important factors in determining the environment experienced during perinatal development. Epidemiological studies and evidence from animal models provide evidence that a mother’s diet and metabolic condition are important in programming the neural circuitry that regulates behavior, resulting in a persistent impact on the offspring’s behavior. Potential mechanisms by which maternal diet and metabolic profile influence the perinatal environment include placental dysfunction and increases in circulating factors such as inflammatory cytokines, nutrients (glucose and fatty acids) and hormones (insulin and leptin). Maternal obesity and high-fat diet (HFD) consumption exposure during development have been observed to increase the risk of developing serious mental health and behavioral disorders including anxiety, depression, attention deficit hyperactivity disorder and autism spectrum disorder. The increased risk of developing these behavioral disorders is postulated to be due to perturbations in the development of neural pathways that regulate behavior, including the serotonergic, dopaminergic and melanocortinergic systems. It is critical to examine the influence that a mother’s nutrition and metabolic profile have on the developing offspring considering the current and alarmingly high prevalence of obesity and HFD consumption in pregnant women.

Maternal high fat diet exposure is associated with increased hepcidin levels, decreased myelination, and neurobehavioral changes in male offspring

“…Although the reasons for the observed sex differences are unclear, our findings could have significant clinical relevance and this is an important point of the present studies. In humans, male offspring experience a disproportionate incidence of neurobehavioral delays and disorders such as autism or ADHD (Rivera et al, 2015; Sullivan et al, 2012). Our data would suggest that males are more sensitive to maternal inflammation and that more robust responses in male verses female offspring account for observed and reported alterations in neurobehavior.…”

Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)

“…These processes are known to be vulnerable to a large number of adverse environmental factors associated with an increased risk of neurological and psychiatric disorders in later life (11)(12)(13)(14)(15)(16).…”

Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring

“…Anxiety behaviour in rodents can be directly associated with inflammatory gene expression and inflammation in brain regions regulating HPA axis response to stress (Dantzer et al, 2008;Rodgers et al, 2012). Adult offspring exposed to maternal HFD exhibit increased anxiety during behavioural tests in the open field and elevated plus maze (Bilbo and Tsang, 2010;Sasaki et al, 2014;Sasaki et al, 2013;Sullivan et al, 2012). Future behavioural work is necessary to assess whether anti-inflammatory responses that are robustly activated upon physiological (CORT) and immune triggers (LPS) during adulthood seen in this study, may attenuate anxiety-like behaviour in offspring with perinatal HFD exposure.…”

“…The mechanisms by which exposure to maternal high-fat diet (HFD) alter inflammatory gene expression in brain regions involved with regulating anxiety behaviour is not well understood. In rodent models of maternal obesity, HFD exposure results in increased anxiety-like behaviour in the Open field and Elevated plus maze tasks at adulthood, accompanied by changes associated with the hypothalamic-pituitary-adrenal (HPA) axis, the neuroendocrine system that regulates stress responses (Bilbo and Tsang, 2010;Peleg-Raibstein et al, 2012;Sasaki et al, 2013;Sullivan et al, 2012). In events of stress, the HPA axis leads to the secretion of corticosterone (CORT) in rodents, which binds to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) to mediate behavioural and immune stress responses in limbic brain regions including the amygdala, hippocampus (HPC), as well as the prefrontal cortex (PFC) (Munck and Náray-Fejes-Tóth, 1992;Silverman and Sternberg, 2012).…”