RT Journal Article SR Electronic T1 The Anti-Epileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats JF bioRxiv FD Cold Spring Harbor Laboratory SP 178319 DO 10.1101/178319 A1 Abbi R. Hernandez A1 Caesar M. Hernandez A1 Keila T. Campos A1 Leah M. Truckenbrod A1 Yasemin Sakarya A1 Joseph A. McQuail A1 Christy S. Carter A1 Jennifer L. Bizon A1 Andrew P. Maurer A1 Sara N. Burke YR 2017 UL http://biorxiv.org/content/early/2017/08/18/178319.abstract AB Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens, which produce high levels of circulating ketone bodies, shifting metabolism away from glucose utilization. While ketogenic diets (KD) were initially introduced to suppress seizures, they are garnering attention for their potential to treat a myriad of neurodegenerative and metabolic disorders that are associated with advanced age. The feasibility and physiological impact of implementing a long-term KD in old animals, however, has not been systematically examined. In this study, young and aged rats consumed a calorically- and nutritionally-matched KD or control diet for 12 weeks. All KD-fed rats maintained higher levels of β-hydroxybutyrate (BHB) and lower levels of glucose relative to controls. However, it took the aged rats longer to reach asymptotic levels of BHB compared to young animals. Moreover, KD-fed rats had significantly less visceral white and brown adipose tissue than controls without a loss of lean mass. Interestingly, the KD lead to significant alterations in protein levels of hippocampal transporters for monocarboxylates, glucose and vesicular glutamate and GABA. Most notably, the age-related decline in vesicular glutamate transporter expression was reversed by the KD. These data demonstrate the feasibility and potential benefits of KDs for treating age-associated neural dysfunction.