Cell - Mu-Opioid Receptors and Dietary Protein Stimulate a Gut-Brain Neural Circuitry Limiting Food Intake

Cell - Mu-Opioid Receptors and Dietary Protein Stimulate a Gut-Brain Neural Circuitry Limiting Food Intake

 Mu-Opioid Receptors and Dietary Protein Stimulate a Gut-Brain Neural Circuitry Limiting Food Intake

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• Graphical Abstract

Cell, 05 July 2012
Copyright 2012 Elsevier Inc. All rights reserved.
10.1016/j.cell.2012.05.039

Authors

Celine Duraffourd, Filipe De Vadder, Daisy Goncalves, Fabien Delaere, Armelle Penhoat, Bleuenn Brusset, Fabienne Rajas, Dominique Chassard, Adeline Duchampt, Anne Stefanutti, Amandine Gautier-Stein, Gilles MithieuxSee Affiliations

• Hint: Rollover Authors and Affiliations
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Institut National de la Santé et de la Recherche Médicale, U 855, Lyon 69372, France Université de Lyon, Lyon 69008, France Université Lyon 1, Villeurbanne 69622, France Hospices Civils de Lyon, HFME, Bron 69250, France Corresponding author These authors contributed equally to this work

• Highlights
• Peptides derived from digested food protein are released in the portal vein
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• They act as antagonists of -opioid receptors present in neurons of the vein walls
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• Ascending nerves in the vagus nerve and the spinal cord signal to the brain
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• These signals promote gut gluconeogenesis and inhibition of food intake

Summary

Intestinal gluconeogenesis is involved in the control of food intake.
We show that mu-opioid receptors (MORs) present in nerves in
the portal vein walls respond to peptides to regulate a gut-brain
neural circuit that controls intestinal gluconeogenesis and satiety.
In vitro, peptides and protein digests behave as MOR antagonists
in competition experiments. In vivo, they stimulate
 MOR-dependent induction of intestinal gluconeogenesis via
activation of brain areas receiving inputs from gastrointestinal
ascending nerves. MOR-knockout mice do not carry out intestinal
 gluconeogenesis in response to peptides and are insensitive to the
 satiety effect induced by protein-enriched diets. Portal infusions of
 MOR modulators have no effect on food intake in mice deficient
for intestinal gluconeogenesis. Thus, the regulation of portal MORs
by peptides triggering signals to and from the brain to induce intestinal
 gluconeogenesis are links in the satiety phenomenon associated
with alimentary protein assimilation.