For several decades, the ketogenic diet has been studied as a replacement for the western diet for weight management and disease treatment. However, there is a lack of understanding regarding the mechanism of change in metabolism induced by the diet. To better understand the diet's physiological effects, we hypothesize that protein turnover in specific organs, like the heart, are modified by the different diets. Therefore, we studied organ protein fractional synthesis rate (FSR) in several organ tissues of mice given ketogenic and a control western diets.
To assess protein FSR of various organs, we studied 4–6 week-old A/J mice) and randomly provided a ketogenic diet (high fat, no carbohydrate, n = 10) or a western diet (high fat, high carbohydrate, n = 10) for 3 months. One day before tissue collection, a D2O bolus was administered via intraperitoneal injection, and mice were provided D2O enriched drinking water to enrich the total body water to about 5% D2O. Eleven tissues (kidney, heart, lung, muscle, fat, jejunum, ileum, liver, brain, skin, and bone) were collected and analyzed for alanine enrichment in the intracellular and protein-bound pool (LC-MS/MS). FSR was calculated as -ln(1-enrichment) as fraction per day. Data are expressed as mean ± SE (unpaired t-test: GraphPad Prism 8.2).
We found a significantly lower heart protein FSR in ketogenic diet compared to the western diet (ketogenic: 0.0795 ± 0.0021, western: 0.0873 ± 0.0015, P = 0.0076). We did not find any difference between protein FSR of the ketogenic and western diet mice in any of the other measured organs.
The ketogenic diet in mice reduces cardiac protein synthesis, which could potentially indicate benefits of a ketogenic diet. We hypothesize that the mechanism of a ketogenic diet to reduce cardiac protein synthesis is via reduced inflammation and normalized heart function (e.g., reduced blood pressure).
Sydney and J.L. Huffines Institute for Sports Medicine, Human Performance Student Research Grant and CTRAL Grant.