Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake.
The American diet, especially that of adolescents, contains highly palatable foods of high-energy content and large amounts of high-fructose sweeteners. These factors are believed to contribute to the obesity epidemic and insulin resistance. Previous investigations revealed that the central metabolism of glucose suppresses food intake mediated by the hypothalamic AMP-kinase/malonyl-CoA signaling system. Unlike glucose, centrally administered fructose increases food intake. Evidence presented herein indicates that the more rapid initial steps of central fructose metabolism deplete hypothalamic ATP level, whereas the slower regulated steps of glucose metabolism elevate hypothalamic ATP level. Consistent with effects on the [ATP]/[AMP] ratio, fructose increases phosphorylation/activation of hypothalamic AMP kinase causing phosphorylation/inactivation of acetyl-CoA carboxylase, whereas glucose has the inverse effects. The changes provoked by central fructose administration reduce hypothalamic malonyl-CoA level and thereby increase food intake. These findings explain the paradoxical fructose effect on food intake and lend credence to the malonyl-CoA hypothesis.
Cha
Seung Hun
SH
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Wolfgang
Michael
M
Tokutake
Yuka
Y
Chohnan
Shigeru
S
Lane
M Daniel
MD
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation
D001786:Blood Glucose; D009479:Neuropeptides; D005632:Fructose; D000249:Adenosine Monophosphate; D008316:Malonyl Coenzyme A; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase; D000103:Acetyl-CoA Carboxylase; D005947:Glucose