title: Interactions of dietary fat and 2,5-anhydro-D-mannitol on energy metabolism in isolated rat hepatocytes.
abstract: The fructose analog 2,5-anhydro-D-mannitol (2,5-AM) stimulates feeding in rats by reducing ATP content in the liver. These behavioral and metabolic effects occur with rats fed a high-carbohydrate/low-fat (HC/LF) diet, but they are prevented or attenuated when the animals eat high-fat/low-carbohydrate (HF/LC) food. To examine the metabolic bases for this effect of diet, we assessed the actions of 2,5-AM on ATP content, oxygen consumption, and substrate oxidation in isolated hepatocytes from rats fed one of the two diets. Compared with cells from rats fed the HC/LF diet ("HC/LF" cells), cells from rats fed the HF/LC diet ("HF/LC" cells) had similar ATP contents but lower oxygen consumption, decreased fructose, and increased palmitate oxidation. 2,5-AM did not decrease ATP content or oxygen consumption in HF/LC cells as much as it did in HC/LF hepatocytes, and it only affected fructose and palmitate oxidation in HC/LF cells. 31P-NMR spectroscopy indicated that differences in phosphate trapping accounted for differences in depletion of ATP by 2,5-AM. These results suggest that intake of the HF/LC diet prevents the eating response and attenuates the decline in liver ATP by shifting hepatocyte metabolism to favor fat over carbohydrate as an energy-yielding substrate.
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA. hongji@monell.org
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Grazyna
authors.initials: G
authors.lastname: Graczyk-Milbrandt
authors.forename: Mary D
authors.initials: MD
authors.lastname: Osbakken
authors.forename: Mark I
authors.initials: MI
authors.lastname: Friedman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002469:Cell Separation; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005632:Fructose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010168:Palmitates / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D010168:Palmitates; D010758:Phosphorus; D005632:Fructose; D008353:Mannitol; C031765:2,5-anhydromannitol; D000255:Adenosine Triphosphate