Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages

Noriyuki Ouchi, Shinji Kihara, Yukio Arita, Makoto Nishida, Akifumi Matsuyama, Yoshihisa Okamoto, Masato Ishigami, Hiroshi Kuriyama, Ken Kishida, Hitoshi Nishizawa, Kikuko Hotta, Masahiro Muraguchi, Yasukazu Ohmoto, Shizuya Yamashita, Tohru Funahashi, Yuji Matsuzawa

Research output: Contribution to journalArticle

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Abstract

Background - Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery, disease. We previously demonstrated that adiponectin acts as a modulator for pro-inflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results - Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. Conclusions - The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.

Original languageEnglish
Pages (from-to)1057-1063
Number of pages7
JournalCirculation
Volume103
Issue number8
DOIs
Publication statusPublished - 27-02-2001

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Class A Scavenger Receptors
Adiponectin
Adipocytes
Blood Proteins
Macrophages
Lipids
Scavenger Receptors
Foam Cells
Monocytes
Messenger RNA
Lipoprotein Lipase
Cholesterol Esters
Differentiation Antigens
Apolipoproteins E

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Ouchi, Noriyuki ; Kihara, Shinji ; Arita, Yukio ; Nishida, Makoto ; Matsuyama, Akifumi ; Okamoto, Yoshihisa ; Ishigami, Masato ; Kuriyama, Hiroshi ; Kishida, Ken ; Nishizawa, Hitoshi ; Hotta, Kikuko ; Muraguchi, Masahiro ; Ohmoto, Yasukazu ; Yamashita, Shizuya ; Funahashi, Tohru ; Matsuzawa, Yuji. / Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. In: Circulation. 2001 ; Vol. 103, No. 8. pp. 1057-1063.
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title = "Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages",
abstract = "Background - Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery, disease. We previously demonstrated that adiponectin acts as a modulator for pro-inflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results - Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. Conclusions - The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.",
author = "Noriyuki Ouchi and Shinji Kihara and Yukio Arita and Makoto Nishida and Akifumi Matsuyama and Yoshihisa Okamoto and Masato Ishigami and Hiroshi Kuriyama and Ken Kishida and Hitoshi Nishizawa and Kikuko Hotta and Masahiro Muraguchi and Yasukazu Ohmoto and Shizuya Yamashita and Tohru Funahashi and Yuji Matsuzawa",
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Ouchi, N, Kihara, S, Arita, Y, Nishida, M, Matsuyama, A, Okamoto, Y, Ishigami, M, Kuriyama, H, Kishida, K, Nishizawa, H, Hotta, K, Muraguchi, M, Ohmoto, Y, Yamashita, S, Funahashi, T & Matsuzawa, Y 2001, 'Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages', Circulation, vol. 103, no. 8, pp. 1057-1063. https://doi.org/10.1161/01.CIR.103.8.1057

Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. / Ouchi, Noriyuki; Kihara, Shinji; Arita, Yukio; Nishida, Makoto; Matsuyama, Akifumi; Okamoto, Yoshihisa; Ishigami, Masato; Kuriyama, Hiroshi; Kishida, Ken; Nishizawa, Hitoshi; Hotta, Kikuko; Muraguchi, Masahiro; Ohmoto, Yasukazu; Yamashita, Shizuya; Funahashi, Tohru; Matsuzawa, Yuji.

In: Circulation, Vol. 103, No. 8, 27.02.2001, p. 1057-1063.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages

AU - Ouchi, Noriyuki

AU - Kihara, Shinji

AU - Arita, Yukio

AU - Nishida, Makoto

AU - Matsuyama, Akifumi

AU - Okamoto, Yoshihisa

AU - Ishigami, Masato

AU - Kuriyama, Hiroshi

AU - Kishida, Ken

AU - Nishizawa, Hitoshi

AU - Hotta, Kikuko

AU - Muraguchi, Masahiro

AU - Ohmoto, Yasukazu

AU - Yamashita, Shizuya

AU - Funahashi, Tohru

AU - Matsuzawa, Yuji

PY - 2001/2/27

Y1 - 2001/2/27

N2 - Background - Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery, disease. We previously demonstrated that adiponectin acts as a modulator for pro-inflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results - Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. Conclusions - The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.

AB - Background - Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery, disease. We previously demonstrated that adiponectin acts as a modulator for pro-inflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results - Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. Conclusions - The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.

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