Child Health Institute of New Jersey, USA.
Child Health Institute of New Jersey, USA; Department of Psychiatry, Robert Wood Johnson Medical School, USA; Brain Health Institute, Rutgers University, New Brunswick, NJ, USA.
Mol Metab. 2023 May;71:101702. doi: 10.1016/j.molmet.2023.101702. Epub 2023 Mar 8.
Maternal overnutrition is associated with adverse outcomes in offspring, including increased risk for obesity and diabetes. Here, we aim to test the effects of maternal obesity on lateral hypothalamic feeding circuit function and determine the relationship with body weight regulation.
Using a mouse model of maternal obesity, we assessed how perinatal overnutrition affected food intake and body weight regulation in adult offspring. We then used channelrhodopsin-assisted circuit mapping and electrophysiological recordings to assess the synaptic connectivity within an extended amygdala-lateral hypothalamic pathway.
We show that maternal overnutrition during gestation and throughout lactation produces offspring that are heavier than controls prior to weaning. When weaned onto chow, the body weights of over-nourished offspring normalize to control levels. However, when presented with highly palatable food as adults, both male and female maternally over-nourished offspring are highly susceptible to diet-induced obesity. This is associated with altered synaptic strength in an extended amygdala-lateral hypothalamic pathway, which is predicted by developmental growth rate. Additionally, lateral hypothalamic neurons receiving synaptic input from the bed nucleus of the stria terminalis have enhanced excitatory input following maternal overnutrition which is predicted by early life growth rate.
Together, these results demonstrate one way in which maternal obesity rewires hypothalamic feeding circuits to predispose offspring to metabolic dysfunction.
母体营养过剩与后代不良后果有关，包括肥胖和糖尿病风险增加。在这里，我们旨在测试母体肥胖对下丘脑外侧进食回路功能的影响，并确定其与体重调节的关系。
我们使用母体肥胖的小鼠模型，评估围产期营养过剩如何影响成年后代的食物摄入和体重调节。然后，我们使用通道视紫红质辅助电路映射和电生理记录来评估扩展杏仁核-下丘脑外侧通路内的突触连接。
我们表明，妊娠和哺乳期母体营养过剩会产生比对照组断奶前更重的后代。当断奶到普通食物时，营养过剩后代的体重会恢复到对照水平。然而，当成年后提供高可口食物时，雄性和雌性母体营养过剩的后代都极易发生饮食诱导的肥胖。这与扩展杏仁核-下丘脑外侧通路中的突触强度改变有关，这是由发育生长速度预测的。此外，来自终纹床核的突触输入到下丘脑外侧的神经元在母体营养过剩后具有增强的兴奋性输入，这是由早期生活生长速度预测的。
总之，这些结果表明母体肥胖重塑下丘脑进食回路的一种方式，使后代易发生代谢功能障碍。
