Huang Alyssa, Maier Matthew T, Vagena Eirini, Xu Allison W
Diabetes Center, University of California, San Francisco, CA, 94143, USA.
Department of Anatomy, University of California, San Francisco, CA, 94143, USA.
Cell Biosci. 2023 Feb 2;13(1):20. doi: 10.1186/s13578-023-00955-2.
Foraging for food precedes food consumption and is an important component of the overall metabolic programming that regulates feeding. Foraging is governed by central nervous system neuronal circuits but how it is influenced by diet and hormonal signals is still not well understood.
In this study, we show that dietary cholesterol exerted suppressive effects on locomotor activity and that these effects were partially mediated by the neuropeptide Agouti-related protein (AgRP). High dietary cholesterol stimulated intestinal expression of fibroblast growth factor 15 (Fgf15), an ortholog of the human fibroblast growth factor 19 (FGF19). Intracerebroventricular infusion of FGF19 peptide reduced exploratory activity in the open field test paradigm. On the other hand, the lack of dietary cholesterol enhanced exploratory activity in the open field test, but this effect was abolished by central administration of FGF19.
Experiments in this study show that dietary cholesterol suppresses locomotor activity and foraging-like behaviors, and this regulation is in part mediated by AgRP neurons. Dietary cholesterol or the central action of FGF19 suppresses exploratory behaviors, and the anxiogenic effects of dietary cholesterol may be mediated by the effect of FGF19 in the mouse brain. This study suggests that dietary cholesterol and intestinal hormone FGF15/19 signal a satiating state to the brain, thereby suppressing foraging-like behaviors.
觅食先于食物消耗，是调节进食的整体代谢程序的重要组成部分。觅食受中枢神经系统神经元回路控制，但饮食和激素信号如何影响觅食仍未完全清楚。
在本研究中，我们表明饮食中的胆固醇对运动活动具有抑制作用，且这些作用部分由神经肽刺鼠相关蛋白（AgRP）介导。高胆固醇饮食刺激肠道中成纤维细胞生长因子15（Fgf15）的表达，Fgf15是人类成纤维细胞生长因子19（FGF19）的直系同源物。脑室内注入FGF19肽可降低旷场试验范式中的探索活动。另一方面，缺乏饮食胆固醇会增强旷场试验中的探索活动，但这种作用可被中枢给予FGF19消除。
本研究中的实验表明，饮食中的胆固醇会抑制运动活动和类似觅食的行为，且这种调节部分由AgRP神经元介导。饮食中的胆固醇或FGF19的中枢作用会抑制探索行为，饮食胆固醇的致焦虑作用可能由FGF19在小鼠大脑中的作用介导。本研究表明，饮食中的胆固醇和肠道激素FGF15/19向大脑发出饱腹感信号，从而抑制类似觅食的行为。
