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

Brandt, C., Nolte, H., Henschke, S., Engstrom Ruud, L., Awazawa, M., Morgan, D. A., et al. (2018). Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation. Cell, 175(5), 1321-1335 e20. doi:10.1016/j.cell.2018.10.015.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0004-71FB-2 Version Permalink: https://hdl.handle.net/21.11116/0000-0004-71FC-1
Genre: Journal Article

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https://www.ncbi.nlm.nih.gov/pubmed/30445039 (Any fulltext)
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 Creators:
Brandt, C.1, Author
Nolte, H.1, Author
Henschke, S.1, Author
Engstrom Ruud, L.1, Author
Awazawa, M.1, Author
Morgan, D. A.1, Author
Gabel, P.1, Author
Sprenger, H. G.1, Author
Hess, M. E.1, Author
Gunther, S.1, Author
Langer, T.1, Author
Rahmouni, K.1, Author
Fenselau, H.1, Author
Kruger, M.1, Author
Bruning, J. C.1, Author
Affiliations:
1Max Planck Society, ou_persistent13              

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 Abstract: 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. VIDEO ABSTRACT.

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 Dates: 2018-11-152018
 Publication Status: Issued
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 Rev. Type: -
 Identifiers: Other: 30445039
DOI: 10.1016/j.cell.2018.10.015
ISSN: 1097-4172 (Electronic) 0092-8674 (Linking)
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 175 (5) Sequence Number: - Start / End Page: 1321 - 1335 e20 Identifier: -