PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity 1 2 3 4

Background: Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. Objective: The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial insulin sensitivity in obese, insulin-resistant men. Design: In a single-blind, randomized, crossover study, 10 insulin-resistant men consumed 3 high-fat mixed meals (2.6 MJ), which were high in SFAs, MUFAs, or PUFAs. Fasting and postprandial skeletal muscle FA processing was examined by measuring differences in arteriovenous concentrations across the forearm muscle. [ 2 H 2 ]Palmitate was infused intravenously to label endogenous triacylglycerol and FFAs in the circulation, and [U- 13 C]palmitate was added to the meal to label chylomicron-triacylglycerol. Skeletal muscle biopsy samples were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after the SFA meal were significantly higher than those after the PUFA meal ( P = 0.006 and 0.033, respectively). Uptake of triacylglycerol-derived FAs was lower in the postprandial phase after the PUFA meal than after the other meals (AUC 60–240 ; P = 0.02). The fractional synthetic rate of the triacylglycerol, diacylglycerol, and phospholipid pool was higher after the MUFA meal than after the SFA meal. PUFA induced less transcriptional downregulation of oxidative pathways than did the other meals. Conclusion: PUFAs reduced triacylglycerol-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity, a more transcriptional oxidative phenotype, and altered intramyocellular lipid partitioning and may therefore be protective against the development of insulin resistance. This trial was registered at clinicaltrials.gov as NCT01466816.