期刊
ENDOCRINOLOGY
卷 164, 期 3, 页码 -出版社
ENDOCRINE SOC
DOI: 10.1210/endocr/bqad008
关键词
val66Met polymorphism; dietary fat intake; obesity; regulated BDNF release; TrkB activation
This study elucidates the role of brain-derived neurotrophic factor (BDNF) in controlling dietary fat intake. Mice with impaired BDNF release showed overconsumption of high-fat diet (HFD) and developed severe obesity. The results indicate that BDNF release suppresses excess dietary fat intake.
High prevalence of obesity is attributable in part to consumption of highly palatable, fat-rich foods. However, the mechanism controlling dietary fat intake is largely unknown. In this study we investigated the role of brain-derived neurotrophic factor (BDNF) in the control of dietary fat intake in a mouse model that mimics the common human Val-to-Met (Val66Met) polymorphism that impairs BDNF release via the regulated secretory pathway. Bdnf(Met/Met) mice gained weight much faster than wild-type (WT) mice and developed severe obesity due to marked hyperphagia when they were fed HFD. Hyperphagia in these mice worsened when the fat content in their diet was increased. Conversely, mice lacking leptin exhibited similar hyperphagia on chow and HFD. When 2 diets were provided simultaneously, WT and Bdnf(Met/Met) mice showed a comparable preference for the more palatable diet rich in either fat or sucrose, indicating that increased hyperphagia on fat-rich diets in Bdnf(Met/Met) mice is not due to enhanced hedonic drive. In support of this interpretation, WT and Bdnf(Met/Met) mice increased calorie intake to a similar extent during the first day after chow was switched to HFD; however, WT mice decreased HFD intake faster than Bdnf(Met/Met) mice in subsequent days. Furthermore, we found that refeeding after fasting or nocturnal feeding with HFD activated TrkB more strongly than with chow in the hypothalamus of WT mice, whereas TrkB activation under these 2 conditions was greatly attenuated in Bdnf(Met/Met) mice. These results indicate that satiety factors generated during HFD feeding induce BDNF release to suppress excess dietary fat intake.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据