Inhibition of glucose oxidation by alpha-cyano-4-hydroxycinnamic acid stimulates feeding in rats.
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.
Del Prete
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Institute of Veterinary Physiology, Winterthurerstr 260, CH-8057 Zürich, Switzerland.
Lutz
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TA
Scharrer
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D003373:Coumaric Acids / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D015536:Down-Regulation; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D010276:Parasympatholytics / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D019289:Pyruvic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D003373:Coumaric Acids; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D009004:Monosaccharide Transport Proteins; D010276:Parasympatholytics; C007175:alpha-cyano-4-hydroxycinnamate; D015016:Yohimbine; D001285:Atropine; D019289:Pyruvic Acid; D003847:Deoxyglucose; D010646:Phentolamine