Nutropioids regulate gut-brain circuitry controlling food intake

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.