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Peripheral µ-opioid receptors (MORs) control hunger by regulating a gut-brain circuit. Peptides and proteins activate this MOR-dependent pathway, influencing satiety and food intake.

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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Endocrinology

Background:

  • µ-opioid receptors (MORs) in the brain are known to modulate hunger.
  • The role of peripheral MORs in regulating hunger sensations was previously unknown.

Purpose of the Study:

  • To investigate the role of peripheral MORs in controlling hunger and satiety.
  • To determine if MORs in the portal vein regulate a gut-brain circuit involved in hunger.

Main Methods:

  • Utilized portal infusions of MOR agonists/antagonists in conscious rodents.
  • Employed MOR knockout (MOR-KO) mice and mice deficient in intestinal gluconeogenesis (IGN).
  • Administered peptides and proteins to assess their effect on MOR-dependent IGN.

Main Results:

  • Peripheral MORs in the portal vein regulate a gut-brain circuit for intestinal gluconeogenesis (IGN) induction.
  • Peptides and proteins promote MOR-dependent IGN induction.
  • MOR-KO mice showed no satiety response to protein-enriched diets and were insensitive to peptide effects.
  • MOR modulators had no effect on food intake in mice lacking IGN.

Conclusions:

  • Peripheral MORs, particularly in the portal vein, play a critical role in the gut-brain neural circuit controlling hunger.
  • This MOR-dependent IGN pathway is causally linked to satiety induced by dietary protein.