Yang Mingxin, Singh Arashdeep, de Araujo Alan, McDougle Molly, Ellis Hillary, Décarie-Spain Léa, Kanoski Scott E, de Lartigue Guillaume
Monell Chemical Senses Center, Philadelphia, PA, USA.
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nat Metab. 2025 Feb;7(2):276-296. doi: 10.1038/s42255-024-01194-6. Epub 2025 Jan 15.
The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development. Using activity-dependent genetic capture of nutrient-responsive dHPC neurons, we demonstrate a causal role of both populations in promoting nutrient-specific intake through different mechanisms. Sugar-responsive neurons encoded spatial memory for sugar location, whereas fat-responsive neurons selectively enhanced the preference and motivation for fat intake. Importantly, stimulation of either nutrient-responsive dHPC neurons increased food intake, while ablation differentially impacted obesogenic diet consumption and prevented diet-induced weight gain. Collectively, these findings uncover previously unknown orexigenic circuits underlying macronutrient-specific consumption and provide a foundation for developing potential obesity treatments.
海马体（HPC）已成为控制食物摄入的关键因素，这超出了其在记忆方面的知名作用。虽然先前的研究主要将HPC与食物摄入抑制联系起来，但最近的研究表明它在食欲过程中也发挥作用。在这里，我们在背侧海马体（dHPC）中确定了空间上不同的神经元群体，它们对脂肪或糖作出反应，而脂肪和糖是导致肥胖的强效天然强化物。通过对营养反应性dHPC神经元进行活动依赖的基因捕获，我们证明了这两种群体通过不同机制在促进特定营养素摄入方面的因果作用。糖反应性神经元编码糖位置的空间记忆，而脂肪反应性神经元选择性地增强了对脂肪摄入的偏好和动机。重要的是，刺激任一营养反应性dHPC神经元都会增加食物摄入量，而消融则对致肥胖饮食的消耗产生不同影响，并防止饮食诱导的体重增加。总的来说，这些发现揭示了以前未知的大量营养素特异性消费背后的促食欲回路，并为开发潜在的肥胖治疗方法提供了基础。
