Inhibition of glucose oxidation by alpha-cyano-4-hydroxycinnamic acid stimulates feeding in rats

Physiol Behav. 2004 Jan;80(4):489-98. doi: 10.1016/j.physbeh.2003.10.007.


Alpha-cyano-4-hydroxycinnamic acid (4-CIN, 100-200 mg/kg b.wt.), which impairs glucose oxidation by inhibiting pyruvate transport across the mitochondrial membrane, stimulated feeding in rats following intraperitoneal injection without affecting blood glucose level. Like 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, 4-CIN probably acts mainly on the CNS through activation of alpha(2)-adrenergic receptors, because the feeding response to 4-CIN was eliminated by phentolamine or yohimbine. Unlike feeding elicited by 2-DG, 4-CIN-induced feeding was eliminated by total abdominal (but not hepatic branch) vagotomy. Since peripheral atropinization also blocked 4-CIN-induced feeding, activation of central parasympathetic neurons seems to be involved in 4-CIN-induced feeding. The feeding response to 4-CIN was diminished in rats fed a high-fat diet, probably because metabolic sensors sensing fatty acid oxidation counteract the feeding response to 4-CIN. The results suggest that inhibition of glucose oxidation by blocking pyruvate entry into mitochondria stimulates feeding in rats in particular when fed a high-carbohydrate diet.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Atropine / pharmacology
  • Blood Glucose / metabolism*
  • Coumaric Acids / pharmacology*
  • Deoxyglucose / metabolism
  • Dietary Carbohydrates / metabolism
  • Dietary Fats / metabolism
  • Down-Regulation
  • Drug Interactions
  • Eating / drug effects
  • Feeding Behavior / drug effects*
  • Male
  • Monosaccharide Transport Proteins / antagonists & inhibitors*
  • Monosaccharide Transport Proteins / metabolism
  • Oxidation-Reduction
  • Parasympatholytics / pharmacology
  • Phentolamine / pharmacology
  • Pyruvic Acid / antagonists & inhibitors*
  • Pyruvic Acid / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Vagotomy
  • Yohimbine / pharmacology


  • Adrenergic alpha-Antagonists
  • Blood Glucose
  • Coumaric Acids
  • Dietary Carbohydrates
  • Dietary Fats
  • Monosaccharide Transport Proteins
  • Parasympatholytics
  • alpha-cyano-4-hydroxycinnamate
  • Yohimbine
  • Atropine
  • Pyruvic Acid
  • Deoxyglucose
  • Phentolamine