Bray G A
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA.
Proc Nutr Soc. 2000 Aug;59(3):373-84. doi: 10.1017/s0029665100000422.
Food intake is a regulated system. Afferent signals provide information to the central nervous system, which is the centre for the control of satiety or food seeking. Such signals can begin even before food is ingested through visual, auditory and olfactory stimuli. One of the recent interesting findings is the demonstration that there are selective fatty acid taste receptors on the tongue of rodents. The suppression of food intake by essential fatty acids infused into the stomach and the suppression of electrical signals in taste buds reflect activation of a K rectifier channel (K 1.5). In animals that become fat eating a high-fat diet the suppression of this current by linoleic acid is less than that in animals that are resistant to obesity induced by dietary fat. Inhibition of fatty acid oxidation with either mercaptoacetate (which blocks acetyl-CoA dehydrogenase) or methylpalmoxirate will increase food intake. When animals have a choice of food, mercaptoacetate stimulates the intake of protein and carbohydrate, but not fat. Afferent gut signals also signal satiety. The first of these gut signals to be identified was cholecystokinin (CCK). When CCK acts on CCK-A receptors in the gastrointestinal tract, food intake is suppressed. These signals are transmitted by the vagus nerve to the nucleus tractus solitarius and thence to higher centres including the lateral parabrachial nucleus, amygdala, and other sites. Rats that lack the CCK-A receptor become obese, but transgenic mice lacking CCK-A receptors do not become obese. CCK inhibits food intake in human subjects. Enterostatin, the pentapeptide produced when pancreatic colipase is cleaved in the gut, has been shown to reduce food intake. This peptide differs in its action from CCK by selectively reducing fat intake. Enterostatin reduces hunger ratings in human subjects. Bombesin and its human analogue, gastrin inhibitory peptide (also gastrin-insulin peptide), reduce food intake in obese and lean subjects. Animals lacking bombesin-3 receptor become obese, suggesting that this peptide may also be important. Circulating glucose concentrations show a dip before the onset of most meals in human subjects and rodents. When the glucose dip is prevented, the next meal is delayed. The dip in glucose is preceded by a rise in insulin, and stimulating insulin release will decrease circulating glucose and lead to food intake. Pyruvate and lactate inhibit food intake differently in animals that become obese compared with lean animals. Leptin released from fat cells is an important peripheral signal from fat stores which modulates food intake. Leptin deficiency or leptin receptor defects produce massive obesity. This peptide signals a variety of central mechanisms by acting on receptors in the arcuate nucleus and hypothalamus. Pancreatic hormones including glucagon, amylin and pancreatic polypeptide reduce food intake. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte-stimulating hormone, growth hormone and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides that modulate feeding. beta-Casomorphin, a heptapeptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group, including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines and thyrotropin-releasing hormone, all decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors that relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.
食物摄入是一个受调节的系统。传入信号向中枢神经系统提供信息，中枢神经系统是控制饱腹感或觅食行为的中心。甚至在食物通过视觉、听觉和嗅觉刺激被摄入之前，这些信号就可能开始。最近一项有趣的发现是，在啮齿动物的舌头上存在选择性脂肪酸味觉受体。注入胃中的必需脂肪酸对食物摄入的抑制以及味蕾中电信号的抑制反映了钾整流通道（K1.5）的激活。在食用高脂肪饮食而变胖的动物中，亚油酸对这种电流的抑制作用小于对饮食脂肪诱导的肥胖具有抗性的动物。用巯基乙酸（它阻断乙酰辅酶A脱氢酶）或甲基棕榈酰辅酶A抑制脂肪酸氧化会增加食物摄入。当动物可以选择食物时，巯基乙酸会刺激蛋白质和碳水化合物的摄入，但不会刺激脂肪的摄入。肠道传入信号也能传递饱腹感。第一个被确定的这类肠道信号是胆囊收缩素（CCK）。当CCK作用于胃肠道中的CCK - A受体时，食物摄入会受到抑制。这些信号通过迷走神经传递到孤束核，然后再传递到包括外侧臂旁核、杏仁核等在内的更高层次的中枢。缺乏CCK - A受体的大鼠会变得肥胖，但缺乏CCK - A受体的转基因小鼠不会变得肥胖。CCK会抑制人类受试者的食物摄入。肠抑胃肽是胰脂肪酶在肠道中被切割时产生的五肽，已被证明能减少食物摄入。这种肽的作用与CCK不同，它能选择性地减少脂肪摄入。肠抑胃肽会降低人类受试者的饥饿感评分。蛙皮素及其人类类似物胃抑制肽（也叫胃泌素 - 胰岛素肽）会减少肥胖和瘦受试者的食物摄入。缺乏蛙皮素 - 3受体的动物会变得肥胖，这表明这种肽可能也很重要。在人类受试者和啮齿动物中，大多数进餐开始前循环葡萄糖浓度会下降。当这种葡萄糖下降被阻止时，下一顿饭会延迟。葡萄糖下降之前胰岛素会升高，刺激胰岛素释放会降低循环葡萄糖并导致食物摄入。与瘦动物相比，丙酮酸和乳酸对肥胖动物食物摄入的抑制作用不同。脂肪细胞释放的瘦素是来自脂肪储存的重要外周信号，它调节食物摄入。瘦素缺乏或瘦素受体缺陷会导致严重肥胖。这种肽通过作用于弓状核和下丘脑的受体来发出多种中枢机制的信号。包括胰高血糖素、胰淀素和胰多肽在内的胰腺激素会减少食物摄入。四种垂体肽也会改变食物摄入。血管加压素会减少进食。相反，注射去乙酰化促黑素细胞激素、生长激素和催乳素会导致食物摄入增加。最后，有一组杂类肽会调节进食。β - 酪蛋白吗啡，一种在酪蛋白水解过程中产生的七肽，会刺激实验动物的食物摄入。相比之下，这组中的其他肽，包括降钙素、载脂蛋白A - IV、组氨酰 - 脯氨酸的环化形式、几种细胞因子和促甲状腺激素释放激素，都会减少食物摄入。这些肽中的许多作用于胃肠道或肝脏受体，通过传入迷走神经将信息传递给大脑。作为一个整体，它们为潜在药物开发提供了许多线索。
