Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

Thompson, Jacqueline R.; Gustafsson, Hanna; DeCapo, Madison; Takahashi, Diana; Bagley, Jennifer L.; Dean, Tyler A.; Kievit, Paul; Fair, Damien A.; Sullivan, Elinor L.

doi:10.3389/fendo.2018.00161

Cited by 38 publications

(32 citation statements)

References 87 publications

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“…In offspring, exposure to mHFD rich in saturated fats, and not trans-fats, led to significant weight grain in both sexes at puberty (P20) and in males at adulthood (P60) [8]. Overall, these studies suggest that the as C-C motif chemokine 22) in the blood of the mothers [9]. This study was the first to directly highlight the interplay among metabolic and inflammatory maternal changes resulting from the diet and their consequences on the offspring behaviors.…”

Section: Discussionmentioning

confidence: 76%

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

Bordeleau

Lacabanne

Cossío

et al. 2020

Preprint

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Background Maternal nutrition is critical for proper fetal development. While increased nutrient intake is essential during pregnancy, an excessive consumption of certain nutrients, like fat, can lead to long-lasting detrimental consequences on the offspring. Animal work investigating the consequences of maternal high-fat diet (mHFD) revealed in the offspring a maternal immune activation (MIA) phenotype associated with increased inflammatory signals. This inflammation was proposed as one of the mechanisms causing neuronal circuit dysfunction, notably in the hippocampus, by altering the brain-resident macrophages –microglia. However, the understanding of mechanisms linking inflammation and microglial activities to pathological brain development remains limited. We hypothesized that mHFD-induced inflammation could prime microglia by altering their specific gene expression signature, population density and/or functions. Methods We used an integrative approach combining molecular techniques, confocal and scanning electron microscopy, to investigate the effects of mHFD vs control diet on inflammatory priming, as well as microglial density, distribution, morphology, and ultrastructure in mice. These analyses were performed on the mothers, and/or their adolescent offspring at postnatal day (P) 30. Results Our study revealed that mHFD results in MIA defined by increased circulating levels of interleukin (IL)-6 in the mothers. This phenotype was associated with an exacerbated inflammatory response to peripheral lipopolysaccharide in mHFD-exposed offspring of both sexes. Microglial morphology was also altered and there were increased microglial interactions with astrocytes in the hippocampus CA1 of mHFD-exposed male offspring, as well as decreased microglia-associated extracellular space pockets in the same region of mHFD-exposed offspring of the two sexes. A decreased mRNA expression of the inflammatory-regulating cytokine Tgfb1 and microglial receptors Tmem119, Trem2 and Cx3cr1 was additionally measured in the hippocampus of mHFD-exposed offspring, especially in males. Conclusions Here, we described how dietary habits during pregnancy and nurturing, particularly the consumption of an enriched fat diet, can influence peripheral immune priming in the offspring. We also found that microglia are affected in terms of gene expression signature, morphology and interactions with the hippocampal parenchyma, in a partially sexually dimorphic manner, which may contribute to the adverse neurodevelopmental outcomes on the offspring.

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Section: Discussionmentioning

confidence: 76%

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

Bordeleau

Lacabanne

Cossío

et al. 2020

Preprint

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“…Similarly to hyperoxia, maternal obesity and neonatal HI increase cytokine levels in the offsprings' brain. This was demonstrated in rodent and non-human primate models of obesity 34,154,155 . Moreover, after neonatal hypoxic-ischaemic brain injury in rodents, cerebral levels pro-inflammatory proteins (e.g.…”

Section: Cytokinesmentioning

confidence: 83%

“…However, this seems to contradict other reports demonstrating that HFD leads to signs of anxiety and depression assessed in the elevated plus maze (EPM), open field (OF) and forced swim test in male offspring 32,33 . In addition to rodents, a non-human primate model was used demonstrating that adiposity in pregnancy increases the risk of impulsive and disruptive behaviour 34 . Besides alteration of emotions, cognitive function is reduced with delayed spatial learning, deficits in reference memory and associative learning accompanied by attenuated levels of amino acids in the medial prefrontal cortex and hippocampus 35,36 .…”

Section: Maternal Obesitymentioning

confidence: 99%

“…Besides alteration of emotions, cognitive function is reduced with delayed spatial learning, deficits in reference memory and associative learning accompanied by attenuated levels of amino acids in the medial prefrontal cortex and hippocampus 35,36 . Preclinical studies in rodents and primates suggest abnormal development of the serotonergic and dopaminergic system and obesity-induced inflammation as underlying mechanisms 29,34 . This is supported by human studies demonstrating that maternal obesity is associated with changes in cytokines, hormones and acute-phase proteins in the second trimester and with an increased risk of maternal infection or childhood asthma 37,38 .…”

Section: Maternal Obesitymentioning

confidence: 99%

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Adverse neuropsychiatric development following perinatal brain injury: from a preclinical perspective

et al. 2018

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Perinatal brain injury is a leading cause of death and disability in young children. Recent advances in obstetrics, reproductive medicine and neonatal intensive care have resulted in significantly higher survival rates of preterm or sick born neonates, at the price of increased prevalence of neurological, behavioural and psychiatric problems in later life. Therefore, the current focus of experimental research shifts from immediate injury processes to the consequences for brain function in later life. The aetiology of perinatal brain injury is multi-factorial involving maternal and also labour-associated factors, including not only placental insufficiency and hypoxia-ischaemia but also exposure to high oxygen concentrations, maternal infection yielding excess inflammation, genetic factors and stress as important players, all of them associated with adverse long-term neurological outcome. Several animal models addressing these noxious stimuli have been established in the past to unravel the underlying molecular and cellular mechanisms of altered brain development. In spite of substantial efforts to investigate short-term consequences, preclinical evaluation of the long-term sequelae for the development of cognitive and neuropsychiatric disorders have rarely been addressed. This review will summarise and discuss not only current evidence but also requirements for experimental research providing a causal link between insults to the developing brain and long-lasting neurodevelopmental disorders.

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“…All animals fed the WSD were also given calorically dense treats once per day. Females were allowed to breed seasonally, and gestational age was determined by ultrasound (18,19). Maternal body fat percent was determined by DEXA in nonpregnant females 3 months prior to the start of the breeding season (17).…”

Section: Experimental Animal Modelmentioning

confidence: 99%

Maternal Obesity and Western-style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates

Campodonico-Burnett

Hetrick

Wesolowski³

et al. 2019

Preprint

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AbstractInfants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a nonhuman primate model to investigate whether maternal obesity combined with a western-style diet (WSD) impairs offspring muscle insulin action. Briefly, adult females were fed a control (CON) or WSD prior to and during pregnancy and lactation. Offspring were weaned to a CON or WSD. Muscle glucose uptake and insulin signaling were measured ex vivo in fetal and juvenile offspring. In vivo signaling was evaluated before and after an intravenous insulin bolus just prior to weaning. We find that fetal muscle exposed to maternal WSD had reduced insulin-stimulated glucose uptake and impaired insulin signaling. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and post-weaning WSD. Analysis of insulin signaling activation revealed distinct changes between fetal and post-weaning WSD exposure. We conclude that maternal WSD leads to a persistent decrease in insulin-stimulated glucose uptake in juvenile offspring even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not ameliorate the effects of maternal WSD suggesting earlier interventions may be necessary.

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Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

Cited by 38 publications

References 87 publications

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

Adverse neuropsychiatric development following perinatal brain injury: from a preclinical perspective

Maternal Obesity and Western-style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates

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