Enduring consequences of maternal obesity for brain inflammation and behavior of offspring

Abstract

Obesity is well characterized as a systemic inflammatory condition, and is also associated with cognitive disruption, suggesting a link between the two. We assessed whether peripheral inflammation in maternal obesity may be transferred to the offspring brain, in particular, the hippocampus, and thereby result in cognitive dysfunction. Rat dams were fed a high-saturated-fat diet (SFD), a high-trans-fat diet (TFD), or a low-fat diet (LFD) for 4 wk prior to mating, and remained on the diet throughout pregnancy and lactation. SFD/TFD exposure significantly increased body weight in both dams and pups compared to controls. Microglial activation markers were increased in the hippocampus of SFD/TFD pups at birth. At weaning and in adulthood, proinflammatory cytokine expression was strikingly increased in the periphery and hippocampus following a bacterial challenge [lipopolysaccharide (LPS)] in the SFD/TFD groups compared to controls. Microglial activation within the hippocampus was also increased basally in SFD rats, suggesting a chronic priming of the cells. Finally, there were marked changes in anxiety and spatial learning in SFD/TFD groups. These effects were all observed in adulthood, even after the pups were placed on standard chow at weaning, suggesting these outcomes were programmed early in life.

Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

“…Similar observation has been made for depression-like behavior in FST. This is inconsistent with some others showing that males from pregnant and lactation dams fed to HFD-diet have displayed significant psychiatry disorders (anxiety and depression-like be-behavior) than females [40].…”

The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities

“…19,20 In rat models, maternal peripheral inflammation resulted from highfat diet and obesity and can lead to offspring brain inflammation. 21 Maternal diabetes also induces proinflammatory environments in intrauterine tissues. 22 Both intrauterine inflammation and fetal brain inflammation are implicated in the development of ASD.…”

High-fat diet alters the dopamine and opioid systems: effects across development

“…In animals, maternal consumption of a high-fat diet has been linked to a range of negative CNS outcomes, including increased anxiety-like behaviors, 31,32 decreased hippocampal dendritic arborization, 33 increased hypothalamic neurogenesis of orexigenic neurons (which can drive overeating and increase the obesity risk) 34 and alterations in the expression of serotonergic genes, dopaminergic genes, inflammation-related genes and neuropeptides related to food intake/metabolism. 31,32,34,35 Not all areas of the brain appear to be similarly sensitive to the effects of maternal consumption of a high-fat diet, as arcuate to paraventricular projections are not affected by maternal diet, 36 yet these projections are affected by maternal insulin status, 37 highlighting the complexity of the interactions between maternal environment (diet, obesity, diabetes) and the offspring outcome.…”

“…31,32,34,35 Not all areas of the brain appear to be similarly sensitive to the effects of maternal consumption of a high-fat diet, as arcuate to paraventricular projections are not affected by maternal diet, 36 yet these projections are affected by maternal insulin status, 37 highlighting the complexity of the interactions between maternal environment (diet, obesity, diabetes) and the offspring outcome.…”