BACKGROUND Maternal obesity as a result of high levels of saturated fat (HFD) consumption leads to significant negative health outcomes in both mother and exposed offspring. Offspring exposed to maternal HFD show sex-specific alterations in metabolic, behavioral, and endocrine function, as well as increased levels of basal neuroinflammation that persists into adulthood. There is evidence that psychosocial stress or exogenous administration of corticosterone (CORT) potentiate inflammatory gene expression; however, the response to acute CORT or immune challenge in adult offspring exposed to maternal HFD during perinatal life is unknown. We hypothesize that adult rat offspring exposed to maternal HFD would show enhanced pro-inflammatory gene expression in response to acute administration of CORT and lipopolysaccharide (LPS) compared to control animals, as a result of elevated basal pro-inflammatory gene expression. To test this, we examined the effects of acute CORT and/or LPS exposure on pro and anti-inflammatory neural gene expression in adult offspring (male and female) with perinatal exposure to a HFD or a control house-chow diet (CHD). METHODS Rat dams consumed HFD or CHD for four weeks prior to mating, during gestation, and throughout lactation. All male and female offspring were weaned on to CHD. In adulthood, offspring were 'challenged' with administration of exogenous CORT and/or LPS, and quantitative PCR was used to measure transcript abundance of glucocorticoid receptors and downstream inflammatory markers in the amygdala, hippocampus, and prefrontal cortex. RESULTS In response to CORT alone, male HFD offspring showed increased levels of anti-inflammatory transcripts, whereas in response to LPS alone, female HFD offspring showed increased levels of pro-inflammatory transcripts. In addition, male HFD offspring showed greater pro-inflammatory gene expression and female HFD offspring exhibited increased anti-inflammatory gene expression in response to simultaneous CORT and LPS administration. CONCLUSIONS These findings suggest that exposure to maternal HFD leads to sex-specific changes that may alter inflammatory responses in the brain, possibly as an adaptive response to basal neuroinflammation.

中文翻译：

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母体高脂肪饮食会诱导成年大鼠后代糖皮质激素和炎症信号的性别特异性变化，以响应皮质酮和脂多糖的挑战。


背景技术由于高水平的饱和脂肪（HFD）消耗而导致的母亲肥胖会给母亲和暴露的后代带来严重的负面健康结果。暴露于母体 HFD 的后代在代谢、行为和内分泌功能方面表现出性别特异性的改变，以及持续到成年期的基础神经炎症水平的增加。有证据表明，心理压力或外源性皮质酮 (CORT) 给药会增强炎症基因的表达；然而，在围产期接触母体 HFD 的成年后代对急性 CORT 或免疫挑战的反应尚不清楚。我们假设，与对照动物相比，暴露于母体 HFD 的成年大鼠后代在急性给予 CORT 和脂多糖 (LPS) 时会表现出促炎基因表达增强，这是由于基础促炎基因表达升高。为了测试这一点，我们检查了急性 CORT 和/或 LPS 暴露对围产期暴露于 HFD 或对照家常饮食 (CHD) 的成年后代（男性和女性）促炎和抗炎神经基因表达的影响。方法 母鼠在交配前、妊娠期间和整个哺乳期持续四个星期食用 HFD 或 CHD。所有雄性和雌性后代均因冠心病断奶。成年后，后代面临外源性 CORT 和/或 LPS 的“挑战”，并使用定量 PCR 来测量杏仁核、海马和前额皮质中糖皮质激素受体和下游炎症标记物的转录本丰度。 结果 单独使用 CORT 时，雄性 HFD 后代表现出抗炎转录本水平升高，而单独使用 LPS 时，雌性 HFD 后代表现出促炎转录本水平升高。此外，雄性 HFD 后代表现出更高的促炎基因表达，雌性 HFD 后代在同时给予 CORT 和 LPS 后表现出抗炎基因表达增加。结论 这些发现表明，母亲接触 HFD 会导致性别特异性的变化，可能会改变大脑的炎症反应，这可能是对基础神经炎症的适应性反应。