Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis

Julia Baumgartl, Stephanie Baudler, Maximilian Scherner, Vladimir Babaev, Liza Makowski, Jill Suttles, Marcia McDuffie, Sergio Fazio, C. Ronald Kahn, Gökhan S. Hotamisligil, Wilhelm Krone, MacRae Linton, Jens C. Brüning

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1β expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2-/-ApoE-/- cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalCell Metabolism
Volume3
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Myeloid Cells
Insulin Resistance
Atherosclerosis
Apolipoproteins E
Insulin
Cell Transplantation
Insulin Receptor
Interleukin-1
Vascular Diseases
Liver Transplantation
Type 2 Diabetes Mellitus
Interleukin-6
Macrophages
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Baumgartl, J., Baudler, S., Scherner, M., Babaev, V., Makowski, L., Suttles, J., ... Brüning, J. C. (2006). Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. Cell Metabolism, 3(4), 247-256. https://doi.org/10.1016/j.cmet.2006.02.010

Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. / Baumgartl, Julia; Baudler, Stephanie; Scherner, Maximilian; Babaev, Vladimir; Makowski, Liza; Suttles, Jill; McDuffie, Marcia; Fazio, Sergio; Kahn, C. Ronald; Hotamisligil, Gökhan S.; Krone, Wilhelm; Linton, MacRae; Brüning, Jens C.

In: Cell Metabolism, Vol. 3, No. 4, 04.2006, p. 247-256.

Research output: Contribution to journalArticle

Baumgartl, J, Baudler, S, Scherner, M, Babaev, V, Makowski, L, Suttles, J, McDuffie, M, Fazio, S, Kahn, CR, Hotamisligil, GS, Krone, W, Linton, M & Brüning, JC 2006, 'Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis', Cell Metabolism, vol. 3, no. 4, pp. 247-256. https://doi.org/10.1016/j.cmet.2006.02.010
Baumgartl, Julia ; Baudler, Stephanie ; Scherner, Maximilian ; Babaev, Vladimir ; Makowski, Liza ; Suttles, Jill ; McDuffie, Marcia ; Fazio, Sergio ; Kahn, C. Ronald ; Hotamisligil, Gökhan S. ; Krone, Wilhelm ; Linton, MacRae ; Brüning, Jens C. / Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. In: Cell Metabolism. 2006 ; Vol. 3, No. 4. pp. 247-256.
@article{a6b0d690803644f6a20b067aeb5839cd,
title = "Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis",
abstract = "Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1β expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2-/-ApoE-/- cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.",
author = "Julia Baumgartl and Stephanie Baudler and Maximilian Scherner and Vladimir Babaev and Liza Makowski and Jill Suttles and Marcia McDuffie and Sergio Fazio and Kahn, {C. Ronald} and Hotamisligil, {G{\"o}khan S.} and Wilhelm Krone and MacRae Linton and Br{\"u}ning, {Jens C.}",
year = "2006",
month = "4",
doi = "10.1016/j.cmet.2006.02.010",
language = "English (US)",
volume = "3",
pages = "247--256",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis

AU - Baumgartl, Julia

AU - Baudler, Stephanie

AU - Scherner, Maximilian

AU - Babaev, Vladimir

AU - Makowski, Liza

AU - Suttles, Jill

AU - McDuffie, Marcia

AU - Fazio, Sergio

AU - Kahn, C. Ronald

AU - Hotamisligil, Gökhan S.

AU - Krone, Wilhelm

AU - Linton, MacRae

AU - Brüning, Jens C.

PY - 2006/4

Y1 - 2006/4

N2 - Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1β expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2-/-ApoE-/- cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.

AB - Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1β expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2-/-ApoE-/- cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.

UR - http://www.scopus.com/inward/record.url?scp=33645563765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645563765&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2006.02.010

DO - 10.1016/j.cmet.2006.02.010

M3 - Article

C2 - 16581002

AN - SCOPUS:33645563765

VL - 3

SP - 247

EP - 256

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -