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.


CONCLUSIONS
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.
Department of Psychological Sciences and Ingestive Behavior Research Center, Purdue University, West Lafayette, IN 47907, USA. kkinzig@purdue.edu
Kimberly P
KP
Kinzig
Mary Ann
MA
Honors
Sara L
SL
Hargrave
Brandon M
BM
Davenport
April D
AD
Strader
Donna
D
Wendt
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D055423:Diet, Ketogenic; D002149:Energy Intake / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D011333:Pro-Opiomelanocortin / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D050796:STAT3 Transcription Factor / Q000032:analysis; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis
D020738:Leptin; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D011333:Pro-Opiomelanocortin