Effects of diet and time of the day on serum and CSF leptin levels in Osborne-Mendel and S5B/Pl rats.
OBJECTIVE
To characterize the effects of dietary fat on the diurnal variation in serum and cerebrospinal fluid (CSF) leptin levels in Osborne-Mendel (OM) and S5B/Pl rats and quantitate the dose response to lower doses of leptin administered into the third cerebral ventricle.


METHODS
Rats were fitted with implanted vascular ports or third ventricular cannulas and fed either laboratory chow or one of two semipurified high-fat or low-fat diets. Leptin and insulin were measured by immunoassay.


RESULTS
Serum leptin and insulin levels were positively correlated and had similar patterns of diurnal change. CSF leptin and insulin also had diurnal rhythms, with a peak at 7:00 am, but the diurnal oscillations of leptin and insulin were significantly lower in the S5B/Pl rats than the OM rats. Thus, the ratio of CSF to serum leptin was significantly higher in the S5B/Pl rats than in the OM rats. Dietary fat had no effect on these diurnal patterns. There was a right shift in the dose response to leptin in the OM rats compared with the S5B/P1 rats. S5B/P1 rats treated with leptin had higher signal transduction and translation (STAT-3) mRNA levels compared with pair-fed or saline injected S5B/P1 rats. Hypothalamic suppressors of cytokine signaling mRNA levels were not statistically different between the groups.


CONCLUSIONS
The higher CSF-to-serum leptin ratio in the S5B/P1 rats, the enhanced suppression of food intake and body weight with leptin injections, and the higher STAT-3 activity in these animals suggest that S5B/P1 rats are more sensitive to leptin than OM rats.
Ishihara
Yuri
Y
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA.
White
Christy L
CL
Kageyama
Haruaki
H
Kageyama
Asako
A
York
David A
DA
Bray
George A
GA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004435:Eating / Q000187:drug effects; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011922:Rats, Mutant Strains; D012097:Repressor Proteins / Q000235:genetics; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D003345:Corticosterone