Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet.
Level 3 - non-randomized controlled study
Controlled clinical trial without explicit indication of randomization in the abstract
PubMed 15310747 · doi:10.1152/japplphysiol.00686.2004
What was done
Aerobically trained men were evaluated after a standardized control diet (51% carbohydrate, 29% fat, 20% protein) and a 56-hour eucaloric high-fat, low-carbohydrate diet (HF/LC; 5% carbohydrate, 73% fat, 22% protein). Participants underwent an oral glucose tolerance test (OGTT; 1 g/kg) after each diet, with vastus lateralis muscle biopsies taken pre-OGTT and 75 minutes post-ingestion. Whole-body glucose disposal and skeletal muscle hexokinase, glycogen synthase (GS), pyruvate dehydrogenase (PDH), and PDH kinase (PDK) activities were measured.
What was found
After the HF/LC diet compared with the control diet: - Blood glucose 90-minute AUC increased 2-fold and plasma insulin 90-minute AUC increased 1.25-fold. - Pre-OGTT PDK activity increased from 0.08 +/- 0.02 to 0.19 +/- 0.05 min(-1). - Pre-OGTT PDH activation decreased from 0.79 +/- 0.10 to 0.38 +/- 0.08 mmol acetyl-CoA.kg wet muscle(-1).min(-1). - During OGTT, PDH activation remained lower on the HF/LC diet (0.60 +/- 0.11 vs. 1.04 +/- 0.09 mmol acetyl-CoA.kg(-1).min(-1)), though the magnitude of activation increase was similar across diets. - Pre-OGTT active GS fraction and maximal hexokinase activity did not change.
Why it matters
This study demonstrates that acute carbohydrate restriction reduces glucose tolerance primarily by downregulating muscle carbohydrate oxidation through rapid PDK activation and PDH inhibition, rather than by impairing glycogen synthesis pathways.
Limits
The abstract does not report the sample size, participant ages, or whether diet order was randomized. Findings are restricted to short-term (56-hour) dietary changes in aerobically trained males and may not generalize to females, untrained individuals, or long-term ketogenic adaptations.
Cited by
- supports Severe carbohydrate restriction decreases the expression and enzymatic activity of pyruvate dehydrogenase.