Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Endocrinology. 2018 Jun 1;159(6):2473-2483. doi: 10.1210/en.2018-00131.
Behavioral adaptation to periods of varying food availability is crucial for survival, and agouti-related protein (AgRP) neurons have been associated with entrainment to temporal restricted feeding. We have shown that carnitine acetyltransferase (Crat) in AgRP neurons enables metabolic flexibility and appropriate nutrient partitioning. In this study, by restricting food availability to 3 h/d during the light phase, we examined whether Crat is a component of a food-entrainable oscillator (FEO) that helps link behavior to food availability. AgRP Crat knockout (KO) mice consumed less food and regained less body weight but maintained blood glucose levels during the 25-day restricted feeding protocol. Importantly, we observed no difference in meal latency, food anticipatory activity (FAA), or brown adipose tissue temperature during the first 13 days of restricted feeding. However, as the restricted feeding paradigm progressed, we noticed an increased FAA in AgRP Crat KO mice. The delayed increase in FAA, which developed during the last 12 days of restricted feeding, corresponded with elevated plasma levels of corticosterone and nonesterified fatty acids, indicating it resulted from greater energy debt incurred by KO mice over the course of the experiment. These experiments highlight the importance of Crat in AgRP neurons in regulating feeding behavior and body weight gain during restricted feeding but not in synchronizing behavior to food availability. Thus, Crat within AgRP neurons forms a component of the homeostatic response to restricted feeding but is not likely to be a molecular component of FEO.
行为适应食物供应的变化对于生存至关重要，而 AgRP 神经元与时间限制进食的同步有关。我们已经表明，AgRP 神经元中的肉碱乙酰转移酶（Crat）使代谢具有灵活性并适当分配营养物质。在这项研究中，我们通过在光期内将食物供应限制为每天 3 小时，来研究 Crat 是否是帮助将行为与食物供应联系起来的食物可诱导振荡器（FEO）的组成部分。AgRP Crat 敲除（KO）小鼠在 25 天的限时喂养方案中进食量减少，体重恢复较少，但血糖水平保持不变。重要的是，在限时喂养的前 13 天，我们没有观察到摄食潜伏期、摄食前活动（FAA）或棕色脂肪组织温度的差异。然而，随着限时喂养模式的进展，我们注意到 AgRP Crat KO 小鼠的 FAA 增加。在限时喂养的最后 12 天中，这种 FAA 的延迟增加与皮质酮和非酯化脂肪酸的血浆水平升高相对应，表明这是由于 KO 小鼠在实验过程中产生了更大的能量债务。这些实验强调了 Crat 在 AgRP 神经元中对于调节限时喂养期间的进食行为和体重增加的重要性，但不能使行为与食物供应同步。因此，AgRP 神经元中的 Crat 形成了对限时喂养的稳态反应的组成部分，但不太可能是 FEO 的分子组成部分。
