Do nonesterified fatty acids regulate skeletal muscle protein turnover in humans?

Abstract

We examined whether elevated plasma nonesterified fatty acid (NEFA) levels exert a direct effect on protein metabolism by measuring [2H5]phenylalanine skeletal muscle exchange and whole body turnover. [2H5]phenylalanine was infused (0.5 mg.kg-1 x h-1) for 300 min in seven healthy subjects on two occasions. Intralipid (10%; 30 ml/h) or 0.154 mol/l NaCl was infused in random order from 120 min. Measurements were taken during basal (90-120 min) and infusion (270-300 min) periods. Intralipid infusion increased plasma NEFA levels [1.31 +/- 0.13 vs. 0.49 +/- 0.05 (SE) mmol/l; P < 0.05] and forearm NEFA uptake [45 +/- 76 vs. -51 +/- 44 nmol . 100 ml forearm-1 x min-1; P < 0.05]. Serum insulin and blood ketone body levels were similar with the two treatments. Elevated plasma NEFA levels were associated with a comparable decrease in forearm phenylalanine uptake (11 +/- 2 vs. 17 +/- 2 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05) and release (20 +/- 2 vs. 26 +/- 3 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05). However, there were no significant changes in net forearm phenylalanine exchange and whole body phenylalanine turnover. Therefore, elevated plasma NEFA levels were associated with a comparable decrease in the rates of skeletal muscle protein synthesis and breakdown but did not appear to influence overall protein balance, as assessed using [2H5]phenylalanine.

Blockade of fatty acid oxidation mimics phase II-phase III transition in a fasting bird, the king penguin

“…Thus our results agree with the finding that elevated plasma NEFA levels in fed humans do not exert an independent effect on the overall balance of protein metabolism in skeletal muscles (44). However, Walker et al (44) suggested that NEFA availability itself might have a more chronic and adaptative effect in situations such as starvation. Present and previous results do not support such a possibility.…”

“…Uric acid is the end product of protein degradation in birds, and its plasma level has been shown to be a good index of this degradation in penguins (34). Thus our results agree with the finding that elevated plasma NEFA levels in fed humans do not exert an independent effect on the overall balance of protein metabolism in skeletal muscles (44). However, Walker et al (44) suggested that NEFA availability itself might have a more chronic and adaptative effect in situations such as starvation.…”

“…This suggestion agrees with the finding of an inverse relationship between whole body proteolysis and NEFA availability (40). In contrast, results supporting the view that elevated plasma NEFA do not exert an independent effect on the overall balance of protein metabolism in skeletal muscle have been reported (44). Because a direct regulatory effect of the plasma level of ketone bodies on protein metabolism has been suggested (38), fatty acid (FA) oxidation could affect protein sparing through production of ketone bodies.…”

Muscle Protein Synthesis and Balance Responsiveness to Essential Amino Acids Ingestion in the Presence of Elevated Plasma Free Fatty Acid Concentrations

“…Previous studies performed in a postabsorptive state have reported that the rates of forearm phenylalanine uptake and release were significantly lower (13) or tended to be lower (12) without a significant difference in the overall forearm phenylalanine balance with lipid infusion. These results appear, at least in part, to be different from the finding of the present study where an improved muscle protein balance was observed with elevated plasma FFA concentrations.…”

“…For some time, animal studies have provided evidence for a decrease in protein turnover with an elevation in plasma FFA concentrations (10,11). In humans, elevated plasma FFA concentrations decrease amino acid flux (12), and have also been associated with lower rates of protein breakdown and synthesis at the muscle (12,13). Recent mechanistic evidence from animal studies indicates that the translation initiation process of muscle protein synthesis is impaired in the presence of elevated plasma FFA concentrations (14).…”