It is well described that increasing
free fatty acids (FFAs) to high physiological levels reduces
insulin sensitivity. In sedentary humans, intramyocellular
lipid (IMCL) is inversely related to
insulin sensitivity. Since muscle fiber composition affects muscle metabolism, whether FFAs induce IMCL accumulation in a fiber type-specific manner remains unknown. We hypothesized that in the setting of acute FFA elevation by
lipid infusion within the context of a hyperinsulinemic-euglycemic clamp, IMCL will preferentially accumulate in type 1 fibers. Normal-weight participants (n = 57, mean ± SE: age 24 ± 0.6 yr, BMI 22.2 ± 0.3 kg/m2) who were either endurance trained or sedentary by self-report were recruited from the University of Minnesota (n = 31, n = 15 trained) and University of Pittsburgh (n = 26, n = 14 trained). All participants underwent a hyperinsulinemic-euglycemic clamp in the context of a 6-h infusion of either
lipid or
glycerol control. A vastus lateralis muscle biopsy was obtained at baseline and end-infusion (6 h). The muscle biopsies were processed and analyzed at the University of Pittsburgh for fiber type-specific IMCL accumulation by
Oil-Red-O staining. Regardless of training status, acute elevation of FFAs to high physiological levels (~400-600 meq/l) increased IMCL preferentially in type 1 fibers (+35 ± 11% compared with baseline, +29 ± 11% compared with
glycerol control: P < 0.05). The increase in IMCL correlated with a decline in
insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp (r = -0.32, P < 0.01) independent of training status. Regardless of training status, increase of FFAs to a physiological range within the context of
hyperinsulinemia shows preferential IMCL accumulation in type 1 fibers.NEW & NOTEWORTHY This novel human study examined the effects of FFA elevation in the setting of
hyperinsulinemia on accumulation of fat in specific types of muscle fibers. Within the context of the hyperinsulinemic-euglycemic clamp, we found that an increase of FFAs to a physiological range sufficient to reduce
insulin sensitivity is associated with preferential IMCL accumulation in type 1 fibers.