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Metabolic inhibitors synergistically decrease hepatic energy status and increase food intake.

H Ji1, G Graczyk-Milbrandt, M I Friedman

  • 1Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA. hongji@monell.org

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|June 10, 2000
PubMed
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Combined treatment with metabolic inhibitors 2,5-anhydro-D-mannitol (2,5-AM) and methyl palmoxirate (MP) synergistically increased food intake and reduced hepatic energy status in rats, suggesting integrated metabolic control of feeding behavior.

Area of Science:

  • Metabolic regulation
  • Neuroscience of feeding behavior
  • Hepatic energy metabolism

Background:

  • Metabolic inhibitors 2,5-anhydro-D-mannitol (2,5-AM) and methyl palmoxirate (MP) induce feeding by lowering hepatic energy status.
  • Combined treatment synergistically increases food intake in rats.

Purpose of the Study:

  • To investigate the synergistic effect of combined 2,5-AM and MP treatment on hepatic energy status.
  • To determine if reduced hepatic energy status is a common trigger for feeding behavior induced by these inhibitors.

Main Methods:

  • Administration of 2,5-AM and MP, alone and in combination, to rats.
  • Measurement of food intake and hepatic energy metabolites (ATP, ADP).
  • Assessment of 2,5-AM uptake into the liver.

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Main Results:

  • Combined 2,5-AM and MP treatment significantly increased feeding behavior compared to single-agent treatments.
  • Only the combination treatment led to significant decreases in the hepatic ATP/ADP ratio and phosphorylation potential.
  • 2,5-AM uptake into the liver was not affected by MP treatment.

Conclusions:

  • Reduced hepatic energy status, specifically the ATP/ADP ratio and phosphorylation potential, is a key signal for triggering feeding behavior induced by 2,5-AM and MP.
  • These findings support an integrated metabolic control system for regulating food intake.
  • The synergistic effect on feeding behavior is linked to a synergistic reduction in hepatic energy status.