Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation

Lisa S. Chow, Douglas G. Mashek, Qi Wang, Sam O. Shepherd, Bret H. Goodpaster, John J. Dubé

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalJournal of applied physiology
Issue number1
StatePublished - Jul 2017

Bibliographical note

Funding Information:
This study was supported by National Institutes of Health (NIH) Grant 5K-12-RR-023247 to L. S. Chow; the Minnesota Medical Foundation; the Pennock Family Foundation; the University of Minnesota CTSA (NIH Grant UL1-TR-0001140; National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-084213-01 (to J. J. Dubé); and the University of Pittsburgh CTRC (NIH Grant M01-RR-00056).

Publisher Copyright:
Copyright © 2017 the American Physiological Society.


  • Free fatty acid
  • Insulin sensitivity
  • Intramyocellular lipid
  • Muscle fiber


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