Maternal diet disrupts the placenta-brain axis in a sex-specific manner (original) (raw)
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Enduring consequences of maternal obesity for brain inflammation and behavior of offspring
The FASEB Journal, 2010
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.-Bilbo, S. D., Tsang, V. Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J. 24, 2104 -2115 (2010). www.fasebj.org
Maternal Obesity as a Risk Factor for Brain Development and Mental Health in the Offspring
Neuroscience, 2020
Maternal obesity plays a key role in the health trajectory of the offspring. Although research on this topic has largely focused on the potential of this condition to increase the risk for child obesity, it is becoming more and more evident that it can also significantly impact cognitive function and mental health. The mechanisms underlying these effects are starting to be elucidated and point to the placenta as a critical organ that may mediate changes in the response to stress, immune function and oxidative stress. Long-term effects of maternal obesity may rely upon epigenetic changes in selected genes that are involved in metabolic and trophic regulations of the brain. More recent evidence also indicates the gut microbiota as a potential mediator of these effects. Overall, understanding cause-effect relationships can allow the development of preventive measures that could rely upon dietary changes in the mother and the offspring. Addressing diets appears more feasible than developing new pharmacological targets and has the potential to affect the multiple interconnected physiological pathways engaged by these complex regulations, allowing prevention of both metabolic and mental disorders.
Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms
Obesity is now epidemic worldwide. Beyond associated diseases such as diabetes, obesity is linked to neuropsychiatric disorders such as depression. Alarmingly, maternal obesity and high-fat diet consumption during gestation/lactation may “program” offspring long-term for increased obesity themselves, along with increased vulnerability to mood disorders. We review the evidence that programming of brain and behavior by perinatal diet is propagated by inflammatory mechanisms, as obesity and high-fat diets are independently associated with exaggerated systemic levels of inflammatory mediators. Due to the recognized dual role of these immune molecules (e.g., interleukin [IL]-6, IL-1β) in placental function and brain development, any disruption of their delicate balance with growth factors or neurotransmitters (e.g., serotonin) by inflammation early in life can permanently alter the trajectory of fetal brain development. Finally, epigenetic regulation of inflammatory pathways is a likely candidate for persistent changes in metabolic and brain function as a consequence of the perinatal environment.
Psychoneuroendocrinology, 2015
Maternal diet during pregnancy can impact maternal behavior as well as the intrauterine environment, playing a critical role in programming offspring's physiology. In a preliminary study, we found a strong association between high-fat diet (HFD) during pregnancy and increased cannibalistic episodes and dams' mortality during late pregnancy and parturition. Based upon these data, we hypothesized that HFD during pregnancy could negatively affect neuroendocrine and metabolic regulations occurring during the final stages of pregnancy, thereby disrupting maternal behavior. To test this hypothesis, female C57BL/6J mice were fed HFD or control diet for 11 weeks until three days before the expected delivery date. Basal corticosterone plasma levels and brain levels of c-Fos were measured both before and after delivery, in addition to leptin levels in the adipose tissue. Dam's emotional behavior and social anxiety,
The role of systemic inflammation linking maternal body mass index to neurodevelopment in children
Pediatric research, 2015
Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations.Pediatric Research (2015); doi:10.1038/pr.2015.179.
Nutrients
Obesity is a main risk factor for the onset and the precipitation of many non-communicable diseases. This condition, which is associated with low-grade chronic systemic inflammation, is of main concern during pregnancy leading to very serious consequences for the new generations. In addition to the prominent role played by the adipose tissue, dysbiosis of the maternal gut may also sustain the obesity-related inflammatory milieu contributing to create an overall suboptimal intrauterine environment. Such a condition here generically defined as “inflamed womb” may hold long-term detrimental effects on fetal brain development, increasing the vulnerability to mental disorders. In this review, we will examine the hypothesis that maternal obesity-related gut dysbiosis and the associated inflammation might specifically target fetal brain microglia, the resident brain immune macrophages, altering neurodevelopmental trajectories in a sex-dependent fashion. We will also review some of the most...
Journal of Neuroscience, 2010
Childhood obesity is associated with increased risk of behavioral/psychological disorders including depression, anxiety, poor learning, and attention deficient disorder. As the majority of women of child-bearing age are overweight or obese and consume a diet high in dietary fat, it is critical to examine the consequences of maternal overnutrition on the development of brain circuitry that regulates offspring behavior. Using a nonhuman primate (NHP) model of diet-induced obesity, we found that maternal high-fat diet (HFD) consumption caused perturbations in the central serotonergic system of fetal offspring. In addition, female infants from HFD fed mothers exhibited increased anxiety in response to threatening novel objects. These findings have important clinical implications as they demonstrate that exposure to maternal HFD consumption during gestation, independent of obesity, increases the risk of developing behavioral disorders such as anxiety.
European Journal of Neuroscience, 2021
HFD unveiled a pro-inflammatory phenotype by inducing a specific increase in the above-mentioned cytokines, suggesting that PNS might impinge upon the same mechanisms underlying vulnerability to metabolic challenges at adulthood" has been changed as follows: "Overall, PNS reduced the expression of Bdnf and Tnf- while HFD administered at adulthood counteracted this effect suggesting that PNS impinges upon the same pathways regulating responses to a metabolic challenge at adulthood". The Discussion and the Concluding remarks have been amended by toning down the effect of HFD on the proinflammatory phenotype of the PNS rats. See below. "…HFD feeding, experienced at adulthood, was able to unmask a pro-inflammatory phenotype, inducing an increase in many pro-inflammatory cytokines in those animals that had experienced PNS." This sentence has been changed as follows: "…moreover, HFD feeding, experienced at adulthood, induced an increase in proinflammatory cytokines in those animals that had experienced PNS." "Therefore, we can hypothesise that the increase in the pro-inflammatory cytokines observed as assessed in the prefrontal cortex (Il-1b and Tnf-a)…". This sentence has been changed as follows: "Here we observed a similar blunted activation upon PNS with HFD triggering a response only in PNS subjects (increased Il-1 and Tnf- in the prefrontal cortex and Tnf- in the dorsal and ventral hippocampus)." "We have here provided evidence for PNS to reduce brain plasticity (first hit) setting the stage for increased vulnerability to further insults during life (HFD, second hit) promoting a pro-inflammatory phenotype". This sentence has been changed as follows: "We have here provided evidence for PNS to reduce brain plasticity (first hit) setting the stage for increased vulnerability to further insults during life (HFD, second hit)." 2) The data relating to ghrelin signaling seems out of place. There is no mention of ghrelin signaling or its significance in the introduction. I think there should be more context/rationale mentioned as to why the authors chose to specifically examine ghrelin in the introduction. Ghrelin is not a unique link connecting mood disorders (HPA axis function) and metabolic disorders. In fact, there are a plethora of neuroendocrine signals connecting the two pathophysiologies, including leptin, FGF21, endocannabinoids, etc. It seems out of context to focus in on ghrelin without providing further context. We thank the reviewer for the thorough suggestion, we have added the following at the end of the Introduction paragraph "We specifically assessed in these brain regions levels of Bdnf, Tnf-, Il-6 and Il-.
Journal of Nutritional Biochemistry, 2022
Diets high in fat and sugar induce inflammation throughout the body, particularly along the gut-brain axis; however, the way these changes in immune signaling mediate one another remains unknown. We investigated cytokine changes in the brain and colon following prolonged high fat or sugar diet in female and male adult C57BL/6 mice. Ten weeks of high fat diet increased levels of TNFα, IL-1β, IL-6, IFNγ, and IL-10 in the female hippocampus and altered cytokines in the frontal cortex of both sexes. High sugar diet increased hippocampal cytokines and decreased cytokines in the diencephalon and frontal cortex. In the colon, high fat diet changed cytokine expression in both sexes, while high sugar diet only increased TNFα in males. Causal mediation analysis confirmed that colon IL-10 and IL-6 mediate high fat diet-induced neuroimmune changes in the female hippocampus and male frontal cortex. Additionally, high fat diet increased food consumption and weight gain in both sexes, while high sugar diet decreased male weight gain. These findings reveal a novel causal link between gut and brain inflammation specific to prolonged consumption of high fat, not high sugar, diet. Importantly, this work includes females which have been under-represented in diet research, and demonstrates that diet-induced neuroinflammation varies by brain region between sexes. Furthermore, our data suggest female brains are more vulnerable than males to inflammatory changes following excessive fat and sugar consumption, which may help explain the increased risk of inflammation-associated psychiatric conditions in women who eat a Western Diet rich in both dietary components.
Maternal high-fat diet prevents developmental programming by early life stress
Psychoneuroendocrinology, 2016
Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic-pituitary-adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development.