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Pharmacokinetics and feeding responses to muramyl dipeptide in rats

Sophie Fosset1, Gilles Fromentin, Olivier Rampin

  • 1Unité INRA/INAPG de Physiologie de la Nutrition et du Comportement Alimentaire, Institut National Agronomique de Paris-Grignon, 16 rue Claude Bernard, F-75231, Paris, France.

Physiology & Behavior
|July 2, 2003
PubMed

Insights

Muramyl dipeptide (MDP), a bacterial peptidoglycan subunit, does not affect rat feeding when ingested orally. However, intraperitoneal injection of MDP causes reduced food intake and sickness behavior, suggesting a role in satiety.

Area of Science:

  • Immunology and Microbiology
  • Neuroscience and Behavior

Background:

  • Muramyl dipeptide (MDP) is the minimal active component of bacterial peptidoglycan.
  • MDP is implicated in food intake depression during systemic infections via macrophage hydrolysis of bacteria.
  • Mammals are continuously exposed to endogenous and exogenous MDP, but its gastrointestinal digestion and absorption remain unclear.

Purpose of the Study:

  • To investigate the physiological significance of MDP digestion and absorption in the gastrointestinal tract.
  • To determine the effects of orally administered MDP on feeding patterns and systemic circulation in rats.

Main Methods:

  • Rats were gavaged with MDP (1.5 mg/kg) to assess oral absorption and effects on feeding.
  • Rats received an intraperitoneal injection of a similar MDP dose to evaluate systemic effects.
  • Feeding patterns, meal frequency, feeding rate, and behavioral satiety sequence (BSS) were monitored.

Main Results:

  • Oral gavage of MDP resulted in very low systemic circulation levels and no alteration in feeding patterns.
  • Intraperitoneal injection of MDP led to a significant depression in food intake.
  • MDP injection induced reduced meal frequency, a slower feeding rate, and behavioral changes indicative of satiety and sickness (increased resting, reduced grooming).

Conclusions:

  • The route of MDP administration significantly influences its physiological effects.
  • Oral ingestion of MDP does not appear to impact feeding behavior or reach systemic circulation in significant amounts.
  • The observed hypophagic effect of systemically administered MDP likely stems from induced satiety and sickness behaviors.

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