Fatty acid oxidation affects food intake by altering hepatic energy status.
Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To determine whether a decrease in hepatic fatty acid oxidation triggers this behavioral response, we compared the effects of different doses of methyl palmoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those on in vivo and in vitro liver and muscle metabolism. Administration of 1 mg/kg MP selectively decreased hepatic fatty acid oxidation but did not stimulate food intake. In contrast, feeding behavior increased in rats given 5 or 10 mg/kg MP, which inhibited hepatic fatty acid oxidation to the same extent as did the low dose but in addition suppressed fatty acid oxidation in muscle and produced a marked depletion of liver glycogen. Dose-related increases in food intake tracked dose-related reductions in liver ATP content, ATP-to-ADP ratio, and phosphorylation potential. The findings suggest that a decrease in hepatic fatty acid oxidation can stimulate feeding behavior by reducing hepatic energy production.
Friedman
M I
MI
Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA. friedman@monell.org
Harris
R B
RB
Ji
H
H
Ramirez
I
I
Tordoff
M G
MG
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation; D010949:Plasma / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004852:Epoxy Compounds; D005227:Fatty Acids; D011422:Propionates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C017522:methyl 2-tetradecylglycidate