• 看+闻食物,可瞬时激活小鼠肝脏中的mTOR信号及其下游的Xbp1 mRNA剪接,增加内质网(ER)应激基因表达、促进磷脂酰胆碱合成,从而引起ER发生形态学改变,为即将到来的营养做好适应性准备;
  • 感知食物可使下丘脑中抑制食欲的阿黑皮素原神经元迅速活化,经交感神经(SNA)“通知”肝脏,该过程依赖于黑皮质素4受体;
  • 肝脏中的去甲肾上腺素信号使mTOR和Xbp1信号活化;
  • 对食物的感知经黑皮质素-SNA-mTOR-Xbp1轴,令肝脏ER发生适应性改变。
Cell [IF:38.637]

Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation



2018-11-15, Article

Abstract & Authors:展开

Adaptation of liver to the postprandial state requires coordinated regulation of protein synthesis and folding aligned with changes in lipid metabolism. Here we demonstrate that sensory food perception is sufficient to elicit early activation of hepatic mTOR signaling, Xbp1 splicing, increased expression of ER-stress genes, and phosphatidylcholine synthesis, which translate into a rapid morphological ER remodeling. These responses overlap with those activated during refeeding, where they are maintained and constantly increased upon nutrient supply. Sensory food perception activates POMC neurons in the hypothalamus, optogenetic activation of POMC neurons activates hepatic mTOR signaling and Xbp1 splicing, whereas lack of MC4R expression attenuates these responses to sensory food perception. Chemogenetic POMC-neuron activation promotes sympathetic nerve activity (SNA) subserving the liver, and norepinephrine evokes the same responses in hepatocytes in vitro and in liver in vivo as observed upon sensory food perception. Collectively, our experiments unravel that sensory food perception coordinately primes postprandial liver ER adaption through a melanocortin-SNA-mTOR-Xbp1s axis.

First Authors:
Claus Brandt

Correspondence Authors:
Jens C Bru¨ ning

All Authors:
Claus Brandt,Hendrik Nolte,Sinika Henschke,Linda Engstro¨ m Ruud,Motoharu Awazawa,Donald A Morgan,Paula Gabel,Hans-Georg Sprenger,Martin E Hess,Stefan Gu¨ nther,Thomas Langer,Kamal Rahmouni,Henning Fenselau,Marcus Kru¨ ger,Jens C Bru¨ ning