Wang Feng, Mehta Poonam, Zinter Max, M'Angale Peter, Lê Timmy, Li Huawei, Kim Jason K, Guertin David A, Martin Gilles E, Thomson Travis, Bach Ingolf
bioRxiv. 2025 Jul 29:2025.07.23.666379. doi: 10.1101/2025.07.23.666379.
Energy homeostasis in mice is maintained through coordinated activity among hypothalamic nuclei that regulate food intake and thermogenesis. These processes must adapt to the sleep-wake cycle, yet the underlying pathways, cell types, and molecular mechanisms governing their diurnal regulation remain poorly understood. We show that mice lacking the E3 ubiquitin ligase are lean and resistant to diet-induced obesity, owing to reduced food intake and enhanced brown adipose tissue (BAT) thermogenesis. We identify GABAergic neurons in the suprachiasmatic nucleus (SCN)-components of the central circadian clock-as mediators of these effects. Specifically, in RIP-Cre neurons governs daily thermogenic rhythms, while in vasoactive intestinal peptide (VIP)-expressing neurons modulates diurnal feeding behavior. Thus, is a key regulator of diurnal rhythms controlling energy balance.
小鼠的能量稳态通过调节食物摄入和产热的下丘脑核团之间的协同活动来维持。这些过程必须适应睡眠-觉醒周期,然而,控制它们昼夜调节的潜在途径、细胞类型和分子机制仍知之甚少。我们发现,缺乏E3泛素连接酶的小鼠体型消瘦,对饮食诱导的肥胖具有抵抗力,这是由于食物摄入量减少和棕色脂肪组织(BAT)产热增强所致。我们确定视交叉上核(SCN)(中央昼夜节律时钟的组成部分)中的GABA能神经元是这些作用的介质。具体而言,RIP-Cre神经元中的[未提及具体基因]控制每日产热节律,而血管活性肠肽(VIP)表达神经元中的[未提及具体基因]调节昼夜进食行为。因此,[未提及具体基因]是控制能量平衡的昼夜节律的关键调节因子。