Short-term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated.

Aims: Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross-over design to determine whether FFAs independently influence insulin sensitivity.

Methods: Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion.

Results: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x 10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/- 0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01) and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA (P > 0.05 for both).

Conclusions: Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid-induced insulin resistance.