Abstract
The ketogenic diet (KD) is an efficacious therapy for medically refractory childhood epilepsy that also slows weight gain. We tested the hypothesis that the KD slows weight gain via neurohormones involved in energy homeostasis. We found that juvenile rodents fed a KD had slower weight gain than those fed a standard diet (SD). Rats fed a KD had higher serum leptin levels and lower insulin levels compared with those fed an SD. We investigated the increase in leptin further because this change was the only one consistent with slower weight gain. Although rats fed the SD experienced slower weight gain when calorie restricted, they had serum leptin levels similar to those fed the SD ad libitum. Furthermore, leptin deficient (ob/ob) and leptin receptor deficient (db/db) mice did not show slower weight gain on the KD. All animals on the KD had elevated serum β-hydroxybutyrate (βHB) levels. Thus, ketosis is insufficient and a functioning leptin signaling system appears necessary for the KD to slow weight gain. The increase in leptin may contribute to the anticonvulsant effects of the KD.
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Abbreviations
- βHB:
-
β-hydroxybutyrate
- CD:
-
calorie restricted diet
- db/db:
-
homozygous leptin receptor deficient mice
- DEXA:
-
dual energy x-ray absorptiometry
- KD:
-
ketogenic diet
- ob/ob:
-
homozygous leptin deficient mice
- PD:
-
postnatal day
- SD:
-
standard diet
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We thank Samuel Klein for critically reviewing the manuscript.
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Supported by grants from the National Institutes of Health (NIH) (DK 20579, NS 42774), the Juvenile Diabetes Research Foundation (1-2004-594), and the Washington University McDonnell Center for Cellular and Molecular Neurobiology. The Washington University Diabetes Research and Training Center (NIH DK 20579) and the Washington University Clinical Nutrition Research Center (NIH DK 56341) also provided assistance. This work was performed in a facility supported by the NIH (NCRR C06 RR015502).
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Thio, L., Erbayat-Altay, E., Rensing, N. et al. Leptin Contributes to Slower Weight Gain in Juvenile Rodents on a Ketogenic Diet. Pediatr Res 60, 413–417 (2006). https://doi.org/10.1203/01.pdr.0000238244.54610.27
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DOI: https://doi.org/10.1203/01.pdr.0000238244.54610.27
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