Brandt, Claus ORCID: 0000-0002-7871-7437, Nolte, Hendrik, Henschke, Sinika, Ruud, Linda Engstroem, Awazawa, Motoharu, Morgan, Donald A., Gabel, Paula, Sprenger, Hans-Georg, Hess, Martin E., Guenther, Stefan, Langer, Thomas, Rahmouni, Kamal ORCID: 0000-0001-5136-6748, Fenselau, Henning, Krueger, Marcus and Bruening, Jens C. (2018). Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation. Cell, 175 (5). S. 1321 - 1356. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brandt, ClausUNSPECIFIEDorcid.org/0000-0002-7871-7437UNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henschke, SinikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruud, Linda EngstroemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Awazawa, MotoharuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, Donald A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabel, PaulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sprenger, Hans-GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, Martin E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenther, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahmouni, KamalUNSPECIFIEDorcid.org/0000-0001-5136-6748UNSPECIFIED
Fenselau, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-165655
DOI: 10.1016/j.cell.2018.10.015
Journal or Publication Title: Cell
Volume: 175
Number: 5
Page Range: S. 1321 - 1356
Date: 2018
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REGULATES GLUCOSE-HOMEOSTASIS; AUTONOMIC NERVE ACTIVITY; ENDOPLASMIC-RETICULUM; POMC NEURONS; INSULIN SENSITIVITY; RAT-LIVER; POSTPRANDIAL THERMOGENESIS; TRANSMEMBRANE PROTEIN; TRANSCRIPTION FACTOR; SIGNALING PATHWAYMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16565

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