Abstracts

RATIONALE: Leptin is a neuroregulatory hormone that plays important roles in the control of food intake, energy expenditure, and glucose transport. There has been little investigation of the metabolic factors regulating food intake and energy expenditure in children or animals on the ketogenic diet. We investigated the following hypotheses: (1) leptin levels are altered in rats fed an experimental ketogenic diet, (2) epileptogenesis alters leptin levels. METHODS: Adult male Sprague-Dawley rats (250-300gm, n=6 per dietary group) were placed on an experimental ketogenic diet (KD) or a control diet (CD) as previously described (Epilepsia 38: 750, 1997). After three weeks, rats were implanted stereotaxically with right basolateral amygdala electrodes. Two weeks later (5 weeks after beginning the KD or CD), tail vein blood was obtained for ?-hydroxybutyrate (?-OHB) and leptin levels. ?-OHB was assessed spectrophotometrically and leptin was measured by radioimmunoassay. All rats were then kindled to five consecutive stage V seizures using standard parameters. Twenty minutes following the fifth stage V seizure, blood was obtained again for ?-OHB and leptin. RESULTS: Baseline ?-OHB levels differed significantly in the KD-fed (5.12?0.38 mM) vs CD-fed (0.26?0.01 mM) rats (p<0.0001). Baseline leptin levels did not differ between KD-fed (3.27?0.71 ng/ml) and CD-fed (2.62?0.48 ng/ml) rats (p=0.78). Weight gain was similar between groups. After kindling, ?-OHB levels were unchanged from baseline (KD: 4.88?0.24 mM, CD: 0.22?0.01 mM; p<0.001). After kindling, there was no difference in leptin levels between dietary groups (KD: 3.65?1.2 ng/ml, CD: 2.47?0.69; p=0.42). The pre- versus post-kindling leptin levels did not differ in either the KD or CD groups (KD: p=0.79; CD: p=0.86). CONCLUSIONS: In rats treated with the KD for five weeks, there was no difference in leptin levels compared to control-fed rats. Leptin levels were not altered by kindling in either control-fed or KD-fed rats. The metabolic adaptation to the ketogenic diet does not appear to involve major participation of the leptin system. Supported by The Charlie Foundation To Help Cure Pediatric Epilepsy.