Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet.
Level 4 - case-series / case-control
Prospective single-arm before-and-after dietary intervention without a parallel control group
PubMed 9843740 · doi:10.1152/ajpendo.1998.275.6.E980
What was done
Human subjects consumed a eucaloric low-carbohydrate, high-fat, high-protein diet (5% carbohydrate, 63% fat, 33% protein) for 6 days, compared with their baseline normal diet (52% carbohydrate, 33% fat, 14% protein). Vastus lateralis muscle biopsies were collected at baseline and after 3 and 6 days on the diet. Muscle homogenates and intact extracted mitochondria were analyzed for pyruvate dehydrogenase kinase (PDHK), total and active pyruvate dehydrogenase (PDHa), carnitine palmitoyltransferase I, beta-hydroxyacyl CoA dehydrogenase, citrate synthase activities, and mitochondrial ATP production rates.
What was found
PDHK activity increased from 0.10 ± 0.02 min⁻¹ at baseline to 0.35 ± 0.09 min⁻¹ at 3 days and 0.49 ± 0.06 min⁻¹ at 6 days. Resting PDHa activity decreased from 0.63 ± 0.17 to 0.17 ± 0.04 mmol·min⁻¹·kg⁻¹ at day 6, while total PDH activity was unchanged. No changes were observed in the activities of other measured enzymes (carnitine palmitoyltransferase I, beta-hydroxyacyl CoA dehydrogenase, citrate synthase) or mitochondrial ATP production rates.
Why it matters
This study shows that human skeletal muscle suppresses glucose oxidation during carbohydrate restriction primarily through a rapid, marked upregulation of PDH kinase that phosphorylates and inactivates PDH, rather than by rapidly increasing the maximal capacity of key fatty acid oxidation enzymes.
Limits
The abstract does not state the sample size or participant characteristics (such as sex, age, or fitness level). The study used a single-arm, within-subject design without a concurrent control group, followed participants for only 6 days, and did not assess functional in vivo substrate flux during exercise.
Cited by
- supports Severe carbohydrate restriction decreases the expression and enzymatic activity of pyruvate dehydrogenase.