Effects of a Ketogenic Diet Containing Medium-Chain Triglycerides and Endurance Training on Metabolic Enzyme Adaptations in Rat Skeletal Muscle

Abstract

Long-term intake of a ketogenic diet enhances utilization of ketone bodies, a particularly energy-efficient substrate, during exercise. However, physiological adaptation to an extremely low-carbohydrate diet has been shown to upregulate pyruvate dehydrogenase kinase 4 (PDK4, a negative regulator of glycolytic flux) content in skeletal muscle, resulting in impaired high-intensity exercise capacity. This study aimed to examine the effects of a long-term ketogenic diet containing medium-chain triglycerides (MCTs) on endurance training-induced adaptations in ketolytic and glycolytic enzymes of rat skeletal muscle. Male Sprague-Dawley rats were placed on either a standard diet (CON), a long-chain triglyceride-containing ketogenic diet (LKD), or an MCT-containing ketogenic diet (MKD). Half the rats in each group performed a 2-h swimming exercise, 5 days a week, for 8 weeks. Endurance training significantly increased 3-oxoacid CoA transferase (OXCT, a ketolytic enzyme) protein content in epitrochlearis muscle tissue, and MKD intake additively enhanced endurance training–induced increases in OXCT protein content. LKD consumption substantially increased muscle PDK4 protein level. However, such PDK4 increases were not observed in the MKD-fed rats. In conclusion, long-term intake of ketogenic diets containing MCTs may additively enhance endurance training–induced increases in ketolytic capacity in skeletal muscle without exerting inhibitory effects on carbohydrate metabolism.

Do Lower-Carbohydrate Diets Increase Total Energy Expenditure? An Updated and Reanalyzed Meta-Analysis of 29 Controlled-Feeding Studies

“…But even with total elimination of dietary carbohydrate (e.g., fasting), the concentration of BOHB rises slowly, reaching steady state only after 2 to 3 wk ( 14 ). Further adaptations that may occur over weeks to months relate to the efficiency of BOHB transport into the brain ( 15 ), changes in muscle and liver metabolism ( 16–18 ), mitochondrial number and function ( 19 , 20 ) oxidative stress and inflammation ( 19–21 ), and hormonal responses ( 22 , 23 ). In time-course studies, negative nitrogen balance (indicative of lean mass loss) ( 24–26 ), fatigue ( 27 ), increased hunger ( 28 ), and decreased exercise tolerance ( 18 ) are characteristically observed with initiation of a ketogenic diet, but these adverse responses typically resolve after a few weeks.…”

Role of Haptoglobin as a Marker of Muscular Improvement in Patients with Multiple Sclerosis after Administration of Epigallocatechin Gallate and Increase of Beta-Hydroxybutyrate in the Blood: A Pilot Study

“…It should be noted that a sustained hemolysis over time, as a consequence of the progression of the disease, is able to saturate the buffering mechanisms of fr-Hb by Hp, which would induce a decrease in its levels, facilitating even more free Hb entry to the CNS through the damaged BBHE [ 38 ], as well as greater muscle destruction. Therefore, the fact that Hp levels, after 4 months of treatment, have not decreased but remain, whereas muscle percentages are increased significantly, could be associated with an improvement in muscular activity, possibly as a consequence of the anabolic effect at a muscular level (both from EGCG [ 21 ] and the increase of BHB prompted by the intake of coconut oil [ 27 ]), being that our hypothesis is that this improvement could be mediated in turn by the neutralization of free HB. As a consequence, this pattern in the secretion of the protein could be associated with its anti-inflammatory effect, as has already been observed in other diseases, as it promotes Hb–Hp binding, thereby inhibiting Hb-stimulated lipid peroxidation and reducing oxidation [ 39 ].…”

“…This would explain its neuroprotective activity against strokes and neurodegenerative diseases [ 25 ]. Additionally, there is evidence on the impact of ketosis, obtained through nutritional diets on anthropometric parameters, leading to a decrease in fat [ 26 ] and being associated with a greater activity of skeletal muscle as a result of the improved energetic performance in the muscles [ 27 ]. This evidence shows that ketogenic diets are used to improve neuromuscular diseases that need to mainly restore skeletal muscle [ 28 ].…”

Effect of Ingestion of Medium-Chain Triglycerides on Substrate Oxidation during Aerobic Exercise Could Depend on Sex Difference in Middle-Aged Sedentary Persons

“…A previous human study has reported an increase in blood triglycerides and an increase in RER during exercise after the 2-week MCTs ingestion [ 34 ], indicating that MCTs intake may promote both carbohydrate assimilation and oxidation. Furthermore, studies using animals have reported inhibition of the increase in pyruvate dehydrogenase kinase 4 protein, which suppressed the glycolytic system on a ketogenic MCTs diet [ 36 ] and increased blood glucose uptake on a high-fat MCTs diet [ 37 ]. The increase in carbohydrate oxidation obtained in the women in the present study may have been due not only to the increase in oxygen uptake by continuous MCTs ingestion but also to the enhancement of glucose metabolism shown in previous studies.…”