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1 Department of Medicine, McMaster University, Hamilton, ON, Canada
2 Department of Biochemistry, McMaster University, Hamilton, ON, Canada
3 Faculty of Applied Health Sciences, Brock University, St Catharines, ON, Canada
* To whom correspondence should be addressed. E-mail: sandra.peters{at}brocku.ca.
We tested the hypothesis that a high fat diet (75% fat; 5% carbohydrates; 20% protein) for which 15% of the fat content was substituted with n-3 fatty acids would not exhibit the diet-induced increase in pyruvate dehydrogenase kinase (PDK) activity which is normally observed in human skeletal muscle. The fat content was the same in both the regular high-fat diet (HF) and in the n-3 substituted diet (N3). PDK activity increased following both high-fat diets, but the increase was attenuated following the N3 diet (0.051 ± 0.007 and 0.218 ± 0.047 for pre- and post-HF respectively; v.s. 0.073 ± 0.016 and 0.133 ± 0.032 min-1 pre- and post-N3). However, the active form of pyruvate dehydrogenase (PDHa) activity decreased to a similar extent in both conditions (0.93 ± 0.17 and 0.43 ± 0.09 pre- and post-HF; vs. 0.87 ± 0.19 and 0.39 ± 0.05 mmol/kg wet weight pre- and post-N3). This suggested that the difference in PDK activity did not affect PDHa activation in the basal state, and it was regulated by intramitochondrial effectors, primarily muscle pyruvate concentration. Muscle glycogen content was consistent throughout the study, before and after both diet conditions, while muscle glucose-6-phosphate, glycerol-3-phosphate, lactate, and pyruvate were decreased after the high-fat diets. Plasma triglycerides decreased following both high-fat diets, but decreased to a greater extent following the N3 diet, while plasma free fatty acids increased following both diets, but to a lesser extent following the N3 diet. In summary, PDK activity is decreased following a high-fat diet which is rich in n-3 fatty acids, although PDHa activity was unaltered. In addition, our data demonstrated that the hypolipidemic effect of n-3 fatty acids occurs earlier (3d) than previously reported and is evident even when the diet has 75% of its total energy is derived from fat.
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