Friedman Mark I
Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA.
Drug News Perspect. 2007 Nov;20(9):573-8. doi: 10.1358/dnp.2007.20.9.1162243.
Despite its well-established role in the control of food intake, the liver has not been a target for the development of drugs to modulate appetite and treat obesity. This paper provides an overview of the hepatic control of food intake and focuses in particular on how it may play a part in overeating and body weight gain. Signals from the liver that control feeding behavior are triggered in response to changes in liver energy status and are carried to the brain by vagal sensory neurons. Consumption of diets rich in fat and carbohydrate is a major contributing cause of overeating and obesity, and susceptibility to such diet-induced obesity is associated with a reduced capacity for fat oxidation. Inhibition of fatty acid oxidation in the liver stimulates food intake by decreasing liver ATP production, suggesting that low liver energy status may contribute to diet-induced overeating and obesity. These findings raise the possibility that liver energy production, the mechanisms that transduce changes in hepatic energy status into neural signals or hepatic vagal afferent activity may provide new targets for the development of drugs for appetite control and obesity.
尽管肝脏在控制食物摄入方面的作用已得到充分确立，但它尚未成为开发调节食欲和治疗肥胖症药物的靶点。本文概述了肝脏对食物摄入的控制，尤其关注其在暴饮暴食和体重增加中可能发挥的作用。控制进食行为的肝脏信号是在肝脏能量状态发生变化时触发的，并通过迷走感觉神经元传递到大脑。富含脂肪和碳水化合物的饮食是暴饮暴食和肥胖的主要促成原因，而对这种饮食诱导的肥胖的易感性与脂肪氧化能力降低有关。肝脏中脂肪酸氧化的抑制通过减少肝脏ATP生成来刺激食物摄入，这表明低肝脏能量状态可能导致饮食诱导的暴饮暴食和肥胖。这些发现提出了一种可能性，即肝脏能量生成、将肝脏能量状态变化转化为神经信号的机制或肝脏迷走神经传入活动可能为开发控制食欲和治疗肥胖症的药物提供新的靶点。
