Showing papers by "Elena Volpi published in 2002"

Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle.

Abstract: Physiological hyperglycemia with hyperinsulinemia reduces fat oxidation in skeletal muscle. The mechanism responsible for this decrease in fat oxidation in human muscle is not known and may contribute to the development of insulin resistance. We hypothesized that the transfer of long-chain fatty acids (LCFAs) into the mitochondria via carnitine palmitoyltransferase-1 (CPT-1) is inhibited by increased malonyl coenzyme A (malonyl-CoA) (a known potent inhibitor of CPT-1) in human muscle during hyperglycemia with hyperinsulinemia. We studied six healthy subjects after an overnight fast and during an induced 5-hour period of hyperglycemia with hyperinsulinemia. Muscle fatty acid oxidation was calculated using stable isotope methodology combined with blood sampling from the femoral artery and vein of one leg. Muscle functional CPT-1 activity was assessed by concurrently infusing an LCFA tracer and a CPT-independent medium-chain fatty acid tracer. Muscle biopsies were obtained from the vastus lateralis after the periods of fasting and hyperglycemia with hyperinsulinemia. Hyperglycemia with hyperinsulinemia decreased LCFA oxidation, but had no effect on LCFA uptake or medium-chain fatty acid oxidation across the leg. Malonyl-CoA concentration significantly increased from 0.13 ± 0.01 to 0.35 ± 0.07 nmol/g during hyperglycemia with hyperinsulinemia. We conclude that hyperglycemia with hyperinsulinemia increases malonyl-CoA, inhibits functional CPT-1 activity, and shunts LCFA away from oxidation and toward storage in human muscle.

Oral and intravenously administered amino acids produce similar effects on muscle protein synthesis in the elderly

Abstract: BACKGROUND: Muscle protein synthesis is stimulated in the elderly when amino acid availability is increased OBJECTIVE: To determine which mode of delivery of amino acids (intravenous vs oral ingestion) is more effective in stimulating the rate of muscle protein synthesis in elderly subjects DESIGN: Fourteen elderly subjects were assigned to one of two groups Following insertion of femoral arterial and venous catheters, subjects were infused with a primed, continuous infusion of L-[ring- 2 H 5 ] phenylalanine Blood samples and muscle biopsies were obtained to measure muscle protein fractional synthesis rate (FSR) with the precursor-product model, phenylalanine kinetics across the leg with the three-pool model, and whole body phenylalanine kinetics Protein metabolism parameters were measured in the basal period, and during the administration of oral amino acids (n=8) or a similar amount of intravenous amino acids (n=6) RESULTS: Enteral and parenteral amino acid administration increased amino acid arterial concentrations and delivery to the leg to a similar extent in both groups Muscle protein synthesis as measured by both FSR, and the three-pool model, increased during amino acid administration (P < 005 vs basal) in both groups with no differences between groups Whole body proteolysis did not change with the oral amino acids whereas it increased slightly during parenteral amino acid administration CONCLUSIONS: Increased amino acid availability stimulates the rate of muscle protein synthesis independent of the route of administration (enteral vs parenteral)