Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man

John N. Clore, Paul A. Harris, Jing Li, Amin Azzam, Ranjodh Gill, Wilhelm Zuelzer, William B. Rizzo, William G. Blackard

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic- euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 ± 7.5 to 64.6 ± 9.0 μU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% ± 0.3% to 21.7% ± 0.4%, P < .05) and decreases in 18:0 (6.2% ± 0.5% to 5.1% ± 0.4%, P = .01), long-chain n-3 fatty acids (1.7% ± 0.2% to 1.4% ± 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% ± 0.8% to 8.0% ± 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man. (C) 2000 by W.B. Saunders Company.

Original languageEnglish (US)
Pages (from-to)232-238
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume49
Issue number2
DOIs
StatePublished - Jan 1 2000

Fingerprint

Phosphatidylcholines
Skeletal Muscle
Fatty Acids
Niacin
Insulin
Insulin Resistance
Phospholipids
Unsaturated Fatty Acids
Membranes
Glucose Clamp Technique
Quadriceps Muscle
Omega-3 Fatty Acids
Muscle Cells
Animal Models
Cell Membrane
Biopsy
Therapeutics
phosphatidylethanolamine

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man. / Clore, John N.; Harris, Paul A.; Li, Jing; Azzam, Amin; Gill, Ranjodh; Zuelzer, Wilhelm; Rizzo, William B.; Blackard, William G.

In: Metabolism: Clinical and Experimental, Vol. 49, No. 2, 01.01.2000, p. 232-238.

Research output: Contribution to journalArticle

Clore, John N. ; Harris, Paul A. ; Li, Jing ; Azzam, Amin ; Gill, Ranjodh ; Zuelzer, Wilhelm ; Rizzo, William B. ; Blackard, William G. / Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man. In: Metabolism: Clinical and Experimental. 2000 ; Vol. 49, No. 2. pp. 232-238.
@article{c73d6fffaf084bf0a70bf32809c7ab06,
title = "Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man",
abstract = "The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic- euglycemic clamp. Treatment with NA was associated with a 25{\%} increase in the half-maximal insulin concentration ([ED50] 52.0 ± 7.5 to 64.6 ± 9.0 μU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21{\%} ± 0.3{\%} to 21.7{\%} ± 0.4{\%}, P < .05) and decreases in 18:0 (6.2{\%} ± 0.5{\%} to 5.1{\%} ± 0.4{\%}, P = .01), long-chain n-3 fatty acids (1.7{\%} ± 0.2{\%} to 1.4{\%} ± 0.1{\%}, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7{\%} ± 0.8{\%} to 8.0{\%} ± 0.8{\%}, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man. (C) 2000 by W.B. Saunders Company.",
author = "Clore, {John N.} and Harris, {Paul A.} and Jing Li and Amin Azzam and Ranjodh Gill and Wilhelm Zuelzer and Rizzo, {William B.} and Blackard, {William G.}",
year = "2000",
month = "1",
day = "1",
doi = "10.1016/S0026-0495(00)91455-0",
language = "English (US)",
volume = "49",
pages = "232--238",
journal = "Metabolism: Clinical and Experimental",
issn = "0026-0495",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man

AU - Clore, John N.

AU - Harris, Paul A.

AU - Li, Jing

AU - Azzam, Amin

AU - Gill, Ranjodh

AU - Zuelzer, Wilhelm

AU - Rizzo, William B.

AU - Blackard, William G.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic- euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 ± 7.5 to 64.6 ± 9.0 μU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% ± 0.3% to 21.7% ± 0.4%, P < .05) and decreases in 18:0 (6.2% ± 0.5% to 5.1% ± 0.4%, P = .01), long-chain n-3 fatty acids (1.7% ± 0.2% to 1.4% ± 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% ± 0.8% to 8.0% ± 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man. (C) 2000 by W.B. Saunders Company.

AB - The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic- euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 ± 7.5 to 64.6 ± 9.0 μU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% ± 0.3% to 21.7% ± 0.4%, P < .05) and decreases in 18:0 (6.2% ± 0.5% to 5.1% ± 0.4%, P = .01), long-chain n-3 fatty acids (1.7% ± 0.2% to 1.4% ± 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% ± 0.8% to 8.0% ± 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man. (C) 2000 by W.B. Saunders Company.

UR - http://www.scopus.com/inward/record.url?scp=0033960344&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033960344&partnerID=8YFLogxK

U2 - 10.1016/S0026-0495(00)91455-0

DO - 10.1016/S0026-0495(00)91455-0

M3 - Article

C2 - 10690951

AN - SCOPUS:0033960344

VL - 49

SP - 232

EP - 238

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

SN - 0026-0495

IS - 2

ER -