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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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
Volume123
Issue number1
DOIs
StatePublished - Jul 1 2017

Fingerprint

Hyperinsulinism
Nonesterified Fatty Acids
Lipids
Glucose Clamp Technique
Insulin Resistance
Muscles
Glycerol
Biopsy
Quadriceps Muscle
Self Report
Fats
Staining and Labeling
Weights and Measures

Keywords

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

Cite this

Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation. / Chow, Lisa S; Mashek, Douglas; Wang, Qi; Shepherd, Sam O.; Goodpaster, Bret H.; Dubé, John J.

In: Journal of applied physiology, Vol. 123, No. 1, 01.07.2017, p. 71-78.

Research output: Contribution to journalArticle

@article{d82e20e3f342406398fae89e5640364d,
title = "Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation",
abstract = "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.",
keywords = "Free fatty acid, Insulin sensitivity, Intramyocellular lipid, Muscle fiber",
author = "Chow, {Lisa S} and Douglas Mashek and Qi Wang and Shepherd, {Sam O.} and Goodpaster, {Bret H.} and Dub{\'e}, {John J.}",
year = "2017",
month = "7",
day = "1",
doi = "10.1152/japplphysiol.00209.2017",
language = "English (US)",
volume = "123",
pages = "71--78",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation

AU - Chow, Lisa S

AU - Mashek, Douglas

AU - Wang, Qi

AU - Shepherd, Sam O.

AU - Goodpaster, Bret H.

AU - Dubé, John J.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Free fatty acid

KW - Insulin sensitivity

KW - Intramyocellular lipid

KW - Muscle fiber

UR - http://www.scopus.com/inward/record.url?scp=85021891360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021891360&partnerID=8YFLogxK

U2 - 10.1152/japplphysiol.00209.2017

DO - 10.1152/japplphysiol.00209.2017

M3 - Article

C2 - 28450549

AN - SCOPUS:85021891360

VL - 123

SP - 71

EP - 78

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 1

ER -