Carbohydrate refeeding after a high-fat diet rapidly reverses the adaptive increase in human skeletal muscle PDH kinase activity.
Level 4 - case-series / case-control
Single-arm before-and-after experimental study without a separate control group
PubMed 19625693 · doi:10.1152/ajpregu.90604.2008
What was done
Eight healthy male volunteers consumed a standardized 3-day baseline diet (50% carbohydrate, 30% fat, 20% protein) followed by an isocaloric 6-day high-fat, low-carbohydrate diet (5% carbohydrate, 75% fat, 20% protein). Participants then consumed a single high-glycemic index carbohydrate meal (88% carbohydrate, 5% fat, 7% protein) providing approximately one third of daily energy intake. Skeletal muscle biopsies were taken before the high-fat diet, after the 6-day high-fat diet, and at 45 minutes and 3 hours following the carbohydrate refeeding meal to measure pyruvate dehydrogenase kinase (PDK) activity and active pyruvate dehydrogenase (PDHa) activity.
What was found
Following the 6-day high-fat diet, muscle PDK activity increased from 0.08 ± 0.01 min⁻¹ to 0.25 ± 0.02 min⁻¹ (P < 0.001). Carbohydrate refeeding reduced PDK activity to 0.17 ± 0.05 min⁻¹ at 45 minutes (P = 0.014) and 0.11 ± 0.01 min⁻¹ at 3 hours (P = 0.006). PDHa activity decreased from 0.89 ± 0.20 mmol·min⁻¹·kg wet wt⁻¹ before the high-fat diet to 0.32 ± 0.05 mmol·min⁻¹·kg wet wt⁻¹ post-diet (P = 0.007). Carbohydrate refeeding increased PDHa activity transiently at 45 minutes, but PDHa returned to lower values by 3 hours (P = 0.025 compared with baseline).
Why it matters
This demonstrates that dietary fat-induced suppression of pyruvate dehydrogenase in human skeletal muscle is rapidly adaptable and can be substantially reversed within hours by a single high-carbohydrate meal.
Limits
The study had a very small sample size (n = 8) and included only healthy male participants. There was no control group receiving a non-carbohydrate meal or continuing the high-fat diet, and the mechanisms behind the subsequent decline in PDHa activity at 3 hours were not resolved.
Cited by
- supports Severe carbohydrate restriction decreases the expression and enzymatic activity of pyruvate dehydrogenase.