Genetic Val66Met BDNF Variant Increases Hyperphagia on Fat-rich Diets in Mice.
Endocrinology(2023)
Abstract
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. BdnfMet/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 BdnfMet/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 BdnfMet/Met mice is not due to enhanced hedonic drive. In support of this interpretation, WT and BdnfMet/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 BdnfMet/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 BdnfMet/Met mice. These results indicate that satiety factors generated during HFD feeding induce BDNF release to suppress excess dietary fat intake.
MoreTranslated text
Key words
TrkB activation,dietary fat intake,obesity,regulated BDNF release,val66Met polymorphism
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined