Acute changes in the response to peripheral leptin with alteration in the diet composition.
Dietary induced obesity in rodents is associated with a resistance to leptin. We have investigated the hypothesis that dietary fat per se alters the feeding response to peripheral leptin in rats that were fed either their habitual high- or low-fat diet or were naively exposed to the alternative diet. Osborne-Mendel rats were adapted to either high- or low-fat diet. Food-deprived rats were given either leptin (0.5 mg/kg body wt ip) or saline, after which they were provided with either their familiar diet or the alternative diet. Food intake of rats adapted and tested with the low-fat diet was reduced 4 h after leptin injection, whereas rats adapted and tested with a high-fat diet did not respond to leptin. Leptin was injected again 1 and 5 days after the high-fat diet-adapted rats were switched to the low-fat diet. Leptin reduced the food intake on both days. In contrast, when low-fat diet-adapted rats were switched to a high-fat diet, the leptin inhibitory response was present on day 1 but not observed on day 5. Peripheral injection of leptin increased serum corticosterone level and decreased hypothalamic neuropeptide Y mRNA expression in rats fed the low-fat but not the high-fat diet for 20 days. The data suggest that dietary fat itself, rather than obesity, may induce leptin resistance within a short time of exposure to a high-fat diet.
Lin
L
L
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA. linl@pbrc.edu
Martin
R
R
Schaffhauser
A O
AO
York
D A
DA
D000818:Animals; D018752:Diet, Fat-Restricted; D004041:Dietary Fats; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005508:Food Deprivation; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D044405:Receptor, Serotonin, 5-HT2C; D054411:Receptors, Leptin; D011985:Receptors, Serotonin / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D004041:Dietary Fats; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D054411:Receptors, Leptin; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse