Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.
Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.
Peptides. 2021 Apr;138:170492. doi: 10.1016/j.peptides.2020.170492. Epub 2021 Jan 8.
In 1973, Gibbs, Young, and Smith showed that exogenous cholecystokinin (CCK) administration reduces food intake in rats. This initial report has led to thousands of studies investigating the physiological role of CCK in regulating feeding behavior. CCK is released from enteroendocrine I cells present along the gastrointestinal (GI) tract. CCK binding to its receptor CCK1R leads to vagal afferent activation providing post-ingestive feedback to the hindbrain. Vagal afferent neurons' (VAN) sensitivity to CCK is modulated by energy status while CCK signaling regulates gene expression of other feeding related signals and receptors expressed by VAN. In addition to its satiation effects, CCK acts all along the GI tract to optimize digestion and nutrient absorption. Diet-induced obesity (DIO) is characterized by reduced sensitivity to CCK and every part of the CCK system is negatively affected by chronic intake of energy-dense foods. EEC have recently been shown to adapt to diet, CCK1R is affected by dietary fats consumption, and the VAN phenotypic flexibility is lost in DIO. Altered endocannabinoid tone, changes in gut microbiota composition, and chronic inflammation are currently being explored as potential mechanisms for diet driven loss in CCK signaling. This review discusses our current understanding of how CCK controls food intake in conditions of leanness and how control is lost in chronic energy excess and obesity, potentially perpetuating excessive intake.
1973 年，Gibbs、Young 和 Smith 表明外源性胆囊收缩素（CCK）的给药会减少大鼠的食物摄入。这一最初的报告导致了数千项研究，旨在调查 CCK 在调节进食行为中的生理作用。CCK 从沿胃肠道（GI）存在的肠内分泌 I 细胞中释放出来。CCK 与其受体 CCK1R 结合，导致迷走传入神经激活，为后脑提供进食后反馈。迷走传入神经元（VAN）对 CCK 的敏感性受能量状态调节，而 CCK 信号调节 VAN 表达的其他与进食相关的信号和受体的基因表达。除了其饱腹感作用外，CCK 还沿胃肠道发挥作用，以优化消化和营养吸收。饮食诱导的肥胖（DIO）的特征是对 CCK 的敏感性降低，CCK 系统的每个部分都受到慢性摄入高热量食物的负面影响。最近已经表明 EEC 可以适应饮食，CCK1R 受膳食脂肪消耗的影响，而 DIO 中 VAN 的表型灵活性丧失。目前正在探索内源性大麻素张力改变、肠道微生物群落组成变化和慢性炎症作为饮食驱动的 CCK 信号丢失的潜在机制。这篇综述讨论了我们目前对 CCK 如何在瘦素状态下控制食物摄入的理解，以及在慢性能量过剩和肥胖症中控制是如何丢失的，这可能会导致过度摄入。
