Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Int J Obes (Lond). 2020 Dec;44(12):2405-2418. doi: 10.1038/s41366-020-00658-5. Epub 2020 Sep 30.
The prevalence of adolescent obesity has increased dramatically, becoming a serious public health concern. While previous evidence suggests that in utero- and early postnatal overnutrition increases adult-onset obesity risk, the neurobiological mechanisms underlying this outcome are not well understood. Non-neuronal cells play an underestimated role in the physiological responses to metabolic/nutrient signals. Hypothalamic glial-mediated inflammation is now considered a contributing factor in the development and perpetuation of obesity; however, attention on the role of gliosis and microglia activation in other nuclei is still needed.
METHODS/RESULTS: Here, we demonstrate that early life consumption of high-fat/sucrose diet (HFSD) is sufficient to increase offspring body weight, hyperleptinemia and potentially maladaptive cytoarchitectural changes in the brainstem dorsal-vagal-complex (DVC), an essential energy balance processing hub, across postnatal development. Our data demonstrate that pre- and postnatal consumption of HFSD result in increased body weight, hyperleptinemia and dramatically affects the non-neuronal landscape, and therefore the plasticity of the DVC in the developing offspring.
Current findings are very provocative, considering the importance of the DVC in appetite regulation, suggesting that HFSD-consumption during early life may contribute to subsequent obesity risk via DVC cytoarchitectural changes.
青少年肥胖症的患病率急剧上升，成为一个严重的公共卫生问题。虽然先前的证据表明胎儿期和新生儿后期的营养过剩会增加成年后肥胖的风险，但这种结果的神经生物学机制尚不清楚。非神经元细胞在代谢/营养信号的生理反应中发挥着被低估的作用。下丘脑胶质细胞介导的炎症现在被认为是肥胖发展和持续的一个促成因素；然而，人们仍然需要关注神经胶质增生和小胶质细胞激活在其他核中的作用。
方法/结果：在这里，我们证明了在生命早期摄入高脂肪/蔗糖饮食（HFSD）足以增加后代的体重、高瘦素血症，并可能导致脑干背侧迷走复合体（DVC）出现适应性细胞结构改变，而 DVC 是一个重要的能量平衡处理中枢，在整个产后发育过程中都是如此。我们的数据表明，产前和产后摄入 HFSD 会导致体重增加、高瘦素血症，并显著影响非神经元景观，从而影响发育中后代的 DVC 可塑性。
鉴于 DVC 在食欲调节中的重要性，目前的发现非常有启发性，这表明生命早期摄入 HFSD 可能会通过 DVC 细胞结构的改变导致随后的肥胖风险。
