A KETOGENIC DIET INCREASES THE EXPRESSION OF MITOCHONDRIAL UNCOUPLING PROTEINS UCP2, UCP4 AND UCP5/BMCP1 IN MOUSE HIPPOCAMPUS
Abstract number :
2.315
Submission category :
Year :
2003
Submission ID :
3811
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Patrick G. Sullivan, Nancy A. Rippy, Jong M. Rho Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington, KY; Pediatrics, University of California at Irvine, Irvine, CA
We have previously reported that a ketogenic diet (KD) enhances fatty acid-induced respiration and reduces reactive oxygen species production in hippocampus of normal juvenile mice (Epilepsia 2002; 43, Suppl 7). In the present study, we asked which if any of the previously identified brain-localizable mitochondrial uncoupling proteins are involved in mediating these effects.
Normal C3H/FeJ mice were fed either the Bio-Serv F3666 diet (6:1 ratio of [fats:carbohydrate + protein]) or normal rodent chow for 10-14 days beginning at P24-30 (N=6-8 in each group). The Keto-Site[trade] reflectance meter (Stanbio Laboratory) was used to measure blood D-[beta]-hydroxybutyrate (BHB) levels. Antibodies to UCP2, UCP4 and UCP5/BMCP1 (Alpha Diagnostics International) were used for hippocampal quantitative Western blot and immunocytochemical analyses.
Mean BHB levels on day of sacrifice were significantly elevated in the KD-treated group (p[lt]0.05). Western blots revealed significant increases in UCP2, UCP4 and UCP5/BMCP1 (165%, 140% and 160% of control, respectively; all p[lt]0.05). Consistent with these findings, immunocytochemical studies confirmed increased expression of all three uncoupling proteins in the hippocampus, especially in the dentate gyrus in KD-treated animals.
Increases in fatty acid-induced mitochondrial respiration are mediated in part through all three known brain-localizable uncoupling proteins. Thus, the ketogenic diet likely exerts generalized effects on mitochondrial respiration, which in turn decreases reactive oxygen species production and mitochondrial calcium loading, all of which may contribute to a neuroprotective effect.
[Supported by: NIH NS 01974 (J.M.R.), The Charlie Foundation (J.M.R.)]