The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born to obese mothers are at increased risk for a number of health conditions. The mechanisms behind this increased risk are poorly understood. Increased exposure to in-utero inflammation induced by maternal obesity is proposed as an underlying mechanism for neurodevelopmental alterations in offspring. Utilizing a non-human primate model of maternal obesity, we hypothesized that maternal consumption of an obesogenic diet will predict offspring peripheral (e.g., cytokines and chemokines) and central (microglia number) inflammatory outcomes via the diet’s effects on maternal adiposity and maternal inflammatory state during the third trimester. We used structural equation modeling to simultaneously examine the complex associations among maternal diet, metabolic state, adiposity, inflammation, and offspring central and peripheral inflammation. Four latent variables were created to capture maternal chemokines and pro-inflammatory cytokines, and offspring cytokine and chemokines. Model results showed that offspring microglia counts in the basolateral amygdala were associated with maternal diet (β = −0.622, p < 0.01), adiposity (β = 0.593, p < 0.01), and length of gestation (β = 0.164, p < 0.05) but not with maternal chemokines (β = 0.135, p = 0.528) or maternal pro-inflammatory cytokines (β = 0.083, p = 0.683). Additionally, we found that juvenile offspring peripheral cytokines (β = −0.389, p < 0.01) and chemokines (β = −0.298, p < 0.05) were associated with a maternal adiposity-induced decrease in maternal circulating chemokines during the third trimester (β = −0.426, p < 0.01). In summary, these data suggest that maternal diet and adiposity appear to directly predict offspring amygdala microglial counts while maternal adiposity influences offspring peripheral inflammatory outcomes via maternal inflammatory state.

肥胖流行病影响了美国 40% 的成年人，其中大约三分之一的孕妇被归类为肥胖。先前的研究表明，肥胖母亲所生的孩子患多种健康状况的风险增加。人们对这种风险增加背后的机制知之甚少。母亲肥胖引起的子宫内炎症暴露增加被认为是后代神经发育改变的潜在机制。利用母体肥胖的非人类灵长类动物模型，我们假设母体摄入致肥胖饮食将通过饮食对母体肥胖和母体炎症状态的影响来预测后代外周（例如细胞因子和趋化因子）和中枢（小胶质细胞数量）炎症结果在妊娠晚期。我们使用结构方程模型同时检查母体饮食、代谢状态、肥胖、炎症以及后代中枢和外周炎症之间的复杂关联。创建了四个潜在变量来捕获母体趋化因子和促炎细胞因子，以及后代细胞因子和趋化因子。模型结果表明，后代基底外侧杏仁核中的小胶质细胞计数与母体饮食 (β = −0.622，p < 0.01)、肥胖 (β = 0.593，p < 0.01) 和妊娠期长短 (β = 0.164，p < 0.05) 相关) 但与母体趋化因子 (β = 0.135, p = 0.528) 或母体促炎细胞因子 (β = 0.083, p = 0.683) 无关。此外，我们发现幼年后代外周细胞因子 (β = -0.389, p < 0.01) 和趋化因子 (β = -0.298, p < 0)。05) 与妊娠晚期母体肥胖引起的母体循环趋化因子减少有关 (β = -0.426, p < 0.01)。总之，这些数据表明，母亲的饮食和肥胖似乎可以直接预测后代杏仁核小胶质细胞的数量，而母亲的肥胖通过母亲的炎症状态影响后代的外周炎症结果。