^*Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana

Correspondence: George A. Bray Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA . E-mail: brayga@pbrc.edu

^**The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 20 June 2003; Revised  00; Accepted 18 May 2004.

Abstract

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.

Research Methods and Procedures: 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.

Discussion: 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.