Woodward Orla R M, Gribble Fiona M, Reimann Frank, Lewis Jo E
Wellcome Trust - MRC Institute of Metabolic Science Metabolic Research Laboratories, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
J Physiol. 2022 Mar;600(5):1053-1078. doi: 10.1113/JP280581. Epub 2021 Aug 17.
The number of people living with obesity has tripled worldwide since 1975 with serious implications for public health, as obesity is linked to a significantly higher chance of early death from associated comorbidities (metabolic syndrome, type 2 diabetes, cardiovascular disease and cancer). As obesity is a consequence of food intake exceeding the demands of energy expenditure, efforts are being made to better understand the homeostatic and hedonic mechanisms governing food intake. Gastrointestinal peptides are secreted from enteroendocrine cells in response to nutrient and energy intake, and modulate food intake either via afferent nerves, including the vagus nerve, or directly within the central nervous system, predominantly gaining access at circumventricular organs. Enteroendocrine hormones modulate homeostatic control centres at hypothalamic nuclei and the dorso-vagal complex. Additional roles of these peptides in modulating hedonic food intake and/or preference via the neural systems of reward are starting to be elucidated, with both peripheral and central peptide sources potentially contributing to central receptor activation. Pharmacological interventions and gastric bypass surgery for the treatment of type 2 diabetes and obesity elevate enteroendocrine hormone levels and also alter food preference. Hence, understanding of the hedonic mechanisms mediated by gut peptide action could advance development of potential therapeutic strategies for the treatment of obesity and its comorbidities.
自1975年以来，全球肥胖人口数量增长了两倍，这对公共卫生产生了严重影响，因为肥胖与因相关合并症（代谢综合征、2型糖尿病、心血管疾病和癌症）导致的早死几率显著升高有关。由于肥胖是食物摄入量超过能量消耗需求的结果，人们正在努力更好地理解控制食物摄入的稳态和享乐机制。胃肠肽由肠内分泌细胞响应营养和能量摄入而分泌，并通过包括迷走神经在内的传入神经或直接在中枢神经系统内调节食物摄入，主要在室周器官进入。肠内分泌激素调节下丘脑核和背迷走神经复合体的稳态控制中心。这些肽通过奖赏神经系统调节享乐性食物摄入和/或偏好的其他作用正开始被阐明，外周和中枢肽源都可能导致中枢受体激活。用于治疗2型糖尿病和肥胖症的药物干预和胃旁路手术会提高肠内分泌激素水平，也会改变食物偏好。因此，了解由肠肽作用介导的享乐机制可能会推动肥胖症及其合并症潜在治疗策略的发展。
