Extended Ketogenic Diet Is Necessary For Increases In Protein Acetylation

Abstract

Decline in mitochondrial function is associated with a decrease in lifespan. We have previously demonstrated that a long-term ketogenic diet (KD) improves mitochondrial function and longevity. However, a life-long KD is difficult to maintain and an intermittent KD might be more viable long term. PURPOSE: Determine how long it takes before a ketogenic diet alters muscle metabolism so that intermittent diets can be developed. METHODS: Four C57BL/6 mice were fed a control diet or 1 or 7 days of continuous KD. At the time of sacrifice, livers, gastrocnemius, brain and kidneys were extracted and frozen in liquid nitrogen before being powdered and homogenized in sucrose lysis buffer and prepared for western blot analysis to determine total acetylated lysine content, total OXPHOS protein, or acetylated p300 content. RESULTS: Following one day of KD, neither acetylated, nor mitochondrial proteins were different than control diet. By seven days of continuous KD diet, total acetylated proteins increased in the liver, kidney and gastrocnemius muscle. Specifically, acetylation of p300 was 3.4±0.89-fold greater following 7 days of KD. Unlike the other tissues the brain showed no difference in acetylated proteins by 7 days. An increase in mitochondrial mass was only seen in the liver at 7 days of KD. CONCLUSIONS: A short term ketogenic diet can be used to rapidly alter protein acetylation in the liver, kidney and muscle. These data suggest that an intermittent keto diet may be useful in promoting a biochemical change in muscle that promotes mitochondrial function and may benefit long-term muscle function.