Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring

Abstract

Obesity induces a low-grade inflammatory state and has been associated with behavioral and cognitive alterations. Importantly, maternal environmental insults can adversely impact subsequent offspring behavior and have been linked with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (AHDH). It is unknown if maternal obesity significantly alters offspring sociability, a key ASD feature, and if altering maternal diet will provide an efficacious intervention paradigm for behavioral deficits. Here we investigated the impact of maternal high fat diet (HFD) and maternal dietary intervention during lactation on offspring behavior and brain inflammation in mice. We found that maternal HFD increased anxiety and decreased sociability in female offspring. Additionally, female offspring from HFD-fed dams also exhibited increased brain IL-1β and TNFα and microglial activation. Importantly, maternal dietary intervention during lactation was sufficient to alleviate social deficits and brain inflammation. Maternal obesity during gestation alone was sufficient to increase hyperactivity in male offspring, a phenotype that was not ameliorated by dietary intervention. These data suggest that maternal HFD acts as a prenatal/perinatal insult that significantly impacts offspring behavior and inflammation and that dietary intervention during lactation may be an easily translatable, efficacious intervention to offset some of these manifestations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0156-9) contains supplementary material, which is available to authorized users.

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

“…Consistent with other reports, we detected increases in body weight, increases in leptin, but no differences in insulin levels or evidence of insulin resistance in the dams. (Guo and Jen, 1995; Kang et al, 2014; Srinivasan et al, 2006a,b) (Fig. 1A and B).…”

Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions

“…Dietary intervention from before pregnancy or during lactation normalises the increased adiposity and circulating leptin, insulin and triglycerides in weanling offspring, rescues the altered motivation and hyperphagia and partially normalises glucose homeostasis and adipocyte morphology in adulthood (Bayol et al, 2007;Rodriguez et al, 2012;Zambrano et al, 2010). In addition, maternal dietary intervention rescues the increased anxiety and altered social behaviours in female offspring of maternal DIO mice in association with amelioration of central inflammation in these offspring (Kang et al, 2014). However, the same reversal is not seen in male offspring.…”

A Review of the Impact of Maternal Obesity on the Cognitive Function and Mental Health of the Offspring

“…Initial investigations using non-human primates reported that young adult female, but not male, macaques born to mothers fed a high fat diet showed increased anxiety to novel and threatening objects [27]. These findings were supported by rodent experiments that found more anxiolytic behaviors in the elevated plus maze and open field test in 1–3-month old male and/or female offspring born to dams fed a high fat diet before mating and during gestation and lactation compared to offspring born to dams fed a control diet [28,29,30,31]. However, weanling (e.g., post-natal day 23–45) rodents born to obese mothers or those fed a cafeteria diet during lactation exhibit lower levels of anxiety [32,33].…”