Sensitivity to the anorectic effects of leptin is retained in rats maintained on a ketogenic diet despite increased adiposity.

BACKGROUND: Rats maintained on a ketogenic diet (KD; 80% fat, 15% protein, 5% carbohydrate) have increased adiposity and leptin as compared to chow-fed controls (CH; 16% fat, 19% protein, 65% carbohydrate), although body weights and daily caloric intakes do not differ. METHODS: Rats maintained on a KD or CH were assessed for responsivity to intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) leptin. Hypothalamic gene expression was evaluated to determine the effects of KD on proopiomelanocortin (POMC) mRNA expression and components of the leptin-signaling system. RESULTS: Caloric intake by KD rats was decreased at a lower dose of i.p. leptin (100 microg) than was required to reduce intake by CH rats (leptin, caloric intake was reduced in KD rats as compared to intake following i.p. saline; p < 0.05). In a separate experiment to evaluate responsivity to i.c.v. leptin, the minimal dose of leptin required to significantly reduce 24-hour caloric intake did not differ between the groups. In the arcuate nucleus, POMC mRNA was elevated after a lower dose of i.c.v. leptin in KD rats (5 microg) than was required to increase POMC mRNA expression in CH rats (15 microg) or reduce caloric intake in either group. Finally, evaluation of the level of phosphorylated STAT3 (pSTAT3) in the arcuate and SOCS3 mRNA in the hypothalamus revealed significantly more pSTAT3-positive cells and increased SOCS3 mRNA expression at baseline for KD rats, compared to CH, neither of which was further increased following i.p. leptin administration. CONCLUSION: These data demonstrate that despite increased adiposity, leptin and markers of leptin resistance, responsivity to the anorectic effects of exogenous leptin is retainable during maintenance on a KD.

Effects of consuming a high carbohydrate diet after eight weeks of exposure to a ketogenic diet.

BACKGROUND: Ketogenic diets have been utilized for weight loss and improvement in metabolic parameters. The present experiments examined the effects of returning to a chow diet after prolonged ingestion of a ketogenic diet. METHODS: Rats were maintained on chow (CH) or a ketogenic diet (KD) for 8 weeks, after which the KD rats were given access to chow only (KD:CH) for 8 additional weeks. Caloric intake, body weight, and plasma leptin, insulin and ghrelin were measured before and after the dietary switch. RESULTS: After 8 weeks of consuming a ketogenic diet, KD rats had increased adiposity and plasma leptin levels, and reduced insulin, as compared to CH controls. One week after the diet switch, fat pad weight and leptin levels remained elevated, and were normalized to CH controls within 8 weeks of the dietary switch. Switching from KD to chow induced a transient hypophagia, such that KD:CH rats consumed significantly fewer calories during the first week after the dietary switch, as compared to calories consumed by CH rats. This hypophagia was despite significantly increased plasma ghrelin in KD:CH rats. Finally, KD:CH rats developed hyperphagia over time, and during weeks 6-8 after the diet switch consumed significantly more calories per day than did CH-fed controls and gained more weight than CH-fed controls. CONCLUSION: Collectively, these data demonstrate that returning to a carbohydrate-based diet after a period of consuming a ketogenic diet has post-diet effects on caloric intake, body weight gain, and insulin levels.