Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet

Suzhao Li, Yu Sun, Chien Ping Liang, Edward B. Thorp, Seongah Han, Andreas W. Jehle, Viswanathan Saraswathi, Brian Pridgen, Jenny E. Kanter, Rong Li, Carrie L. Welch, Alyssa H. Hasty, Karin E. Bornfeldt, Jan L. Breslow, Ira Tabas, Alan R. Tall

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

RATIONALE:: The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions. OBJECTIVE:: To determine whether there is defective efferocytosis in a mouse model of obesity and atherosclerosis. METHODS AND RESULTS:: We quantified efferocytosis in peritoneal macrophages and in atherosclerotic lesions of obese ob/ob or ob/ob;Ldlr mice and littermate controls. Peritoneal macrophages from ob/ob and ob/ob;Ldlr mice showed impaired efferocytosis, reflecting defective phosphatidylinositol 3-kinase activation during uptake of apoptotic cells. Membrane lipid composition of ob/ob and ob/ob;Ldlr macrophages showed an increased content of saturated fatty acids (FAs) and decreased ω-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) compared to controls. A similar defect in efferocytosis was induced by treating control macrophages with saturated free FA/BSA complexes, whereas the defect in ob/ob macrophages was reversed by treatment with eicosapentaenoic acid/BSA or by feeding ob/ob mice a fish oil diet rich in ω-3 FAs. There was also defective macrophage efferocytosis in atherosclerotic lesions of ob/ob;Ldlr mice and this was reversed by a fish oil-rich diet. CONCLUSIONS:: The findings suggest that in obesity and type 2 diabetes elevated levels of saturated FAs and/or decreased levels of ω-3 FAs contribute to decreased macrophage efferocytosis. Beneficial effects of fish oil diets in atherosclerotic cardiovascular disease may involve improvements in macrophage function related to reversal of defective efferocytosis and could be particularly important in type 2 diabetes and obesity.

Original languageEnglish (US)
Pages (from-to)1072-1082
Number of pages11
JournalCirculation Research
Volume105
Issue number11
DOIs
StatePublished - Nov 1 2009

Fingerprint

Cytophagocytosis
Fish Oils
Macrophages
Diet
Fatty Acids
Type 2 Diabetes Mellitus
Eicosapentaenoic Acid
Obesity
Peritoneal Macrophages
Atherosclerosis
Phosphatidylinositol 3-Kinase
Docosahexaenoic Acids
Membrane Lipids
Nonesterified Fatty Acids
Cause of Death
Cardiovascular Diseases
Inflammation

Keywords

  • Atherosclerosis
  • Efferocytosis
  • Fatty acids
  • Macrophages
  • Mouse

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet. / Li, Suzhao; Sun, Yu; Liang, Chien Ping; Thorp, Edward B.; Han, Seongah; Jehle, Andreas W.; Saraswathi, Viswanathan; Pridgen, Brian; Kanter, Jenny E.; Li, Rong; Welch, Carrie L.; Hasty, Alyssa H.; Bornfeldt, Karin E.; Breslow, Jan L.; Tabas, Ira; Tall, Alan R.

In: Circulation Research, Vol. 105, No. 11, 01.11.2009, p. 1072-1082.

Research output: Contribution to journalArticle

Li, S, Sun, Y, Liang, CP, Thorp, EB, Han, S, Jehle, AW, Saraswathi, V, Pridgen, B, Kanter, JE, Li, R, Welch, CL, Hasty, AH, Bornfeldt, KE, Breslow, JL, Tabas, I & Tall, AR 2009, 'Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet', Circulation Research, vol. 105, no. 11, pp. 1072-1082. https://doi.org/10.1161/CIRCRESAHA.109.199570
Li, Suzhao ; Sun, Yu ; Liang, Chien Ping ; Thorp, Edward B. ; Han, Seongah ; Jehle, Andreas W. ; Saraswathi, Viswanathan ; Pridgen, Brian ; Kanter, Jenny E. ; Li, Rong ; Welch, Carrie L. ; Hasty, Alyssa H. ; Bornfeldt, Karin E. ; Breslow, Jan L. ; Tabas, Ira ; Tall, Alan R. / Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet. In: Circulation Research. 2009 ; Vol. 105, No. 11. pp. 1072-1082.
@article{06832ca0d75a4a04a077aa480186679e,
title = "Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet",
abstract = "RATIONALE:: The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions. OBJECTIVE:: To determine whether there is defective efferocytosis in a mouse model of obesity and atherosclerosis. METHODS AND RESULTS:: We quantified efferocytosis in peritoneal macrophages and in atherosclerotic lesions of obese ob/ob or ob/ob;Ldlr mice and littermate controls. Peritoneal macrophages from ob/ob and ob/ob;Ldlr mice showed impaired efferocytosis, reflecting defective phosphatidylinositol 3-kinase activation during uptake of apoptotic cells. Membrane lipid composition of ob/ob and ob/ob;Ldlr macrophages showed an increased content of saturated fatty acids (FAs) and decreased ω-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) compared to controls. A similar defect in efferocytosis was induced by treating control macrophages with saturated free FA/BSA complexes, whereas the defect in ob/ob macrophages was reversed by treatment with eicosapentaenoic acid/BSA or by feeding ob/ob mice a fish oil diet rich in ω-3 FAs. There was also defective macrophage efferocytosis in atherosclerotic lesions of ob/ob;Ldlr mice and this was reversed by a fish oil-rich diet. CONCLUSIONS:: The findings suggest that in obesity and type 2 diabetes elevated levels of saturated FAs and/or decreased levels of ω-3 FAs contribute to decreased macrophage efferocytosis. Beneficial effects of fish oil diets in atherosclerotic cardiovascular disease may involve improvements in macrophage function related to reversal of defective efferocytosis and could be particularly important in type 2 diabetes and obesity.",
keywords = "Atherosclerosis, Efferocytosis, Fatty acids, Macrophages, Mouse",
author = "Suzhao Li and Yu Sun and Liang, {Chien Ping} and Thorp, {Edward B.} and Seongah Han and Jehle, {Andreas W.} and Viswanathan Saraswathi and Brian Pridgen and Kanter, {Jenny E.} and Rong Li and Welch, {Carrie L.} and Hasty, {Alyssa H.} and Bornfeldt, {Karin E.} and Breslow, {Jan L.} and Ira Tabas and Tall, {Alan R.}",
year = "2009",
month = "11",
day = "1",
doi = "10.1161/CIRCRESAHA.109.199570",
language = "English (US)",
volume = "105",
pages = "1072--1082",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet

AU - Li, Suzhao

AU - Sun, Yu

AU - Liang, Chien Ping

AU - Thorp, Edward B.

AU - Han, Seongah

AU - Jehle, Andreas W.

AU - Saraswathi, Viswanathan

AU - Pridgen, Brian

AU - Kanter, Jenny E.

AU - Li, Rong

AU - Welch, Carrie L.

AU - Hasty, Alyssa H.

AU - Bornfeldt, Karin E.

AU - Breslow, Jan L.

AU - Tabas, Ira

AU - Tall, Alan R.

PY - 2009/11/1

Y1 - 2009/11/1

N2 - RATIONALE:: The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions. OBJECTIVE:: To determine whether there is defective efferocytosis in a mouse model of obesity and atherosclerosis. METHODS AND RESULTS:: We quantified efferocytosis in peritoneal macrophages and in atherosclerotic lesions of obese ob/ob or ob/ob;Ldlr mice and littermate controls. Peritoneal macrophages from ob/ob and ob/ob;Ldlr mice showed impaired efferocytosis, reflecting defective phosphatidylinositol 3-kinase activation during uptake of apoptotic cells. Membrane lipid composition of ob/ob and ob/ob;Ldlr macrophages showed an increased content of saturated fatty acids (FAs) and decreased ω-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) compared to controls. A similar defect in efferocytosis was induced by treating control macrophages with saturated free FA/BSA complexes, whereas the defect in ob/ob macrophages was reversed by treatment with eicosapentaenoic acid/BSA or by feeding ob/ob mice a fish oil diet rich in ω-3 FAs. There was also defective macrophage efferocytosis in atherosclerotic lesions of ob/ob;Ldlr mice and this was reversed by a fish oil-rich diet. CONCLUSIONS:: The findings suggest that in obesity and type 2 diabetes elevated levels of saturated FAs and/or decreased levels of ω-3 FAs contribute to decreased macrophage efferocytosis. Beneficial effects of fish oil diets in atherosclerotic cardiovascular disease may involve improvements in macrophage function related to reversal of defective efferocytosis and could be particularly important in type 2 diabetes and obesity.

AB - RATIONALE:: The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions. OBJECTIVE:: To determine whether there is defective efferocytosis in a mouse model of obesity and atherosclerosis. METHODS AND RESULTS:: We quantified efferocytosis in peritoneal macrophages and in atherosclerotic lesions of obese ob/ob or ob/ob;Ldlr mice and littermate controls. Peritoneal macrophages from ob/ob and ob/ob;Ldlr mice showed impaired efferocytosis, reflecting defective phosphatidylinositol 3-kinase activation during uptake of apoptotic cells. Membrane lipid composition of ob/ob and ob/ob;Ldlr macrophages showed an increased content of saturated fatty acids (FAs) and decreased ω-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) compared to controls. A similar defect in efferocytosis was induced by treating control macrophages with saturated free FA/BSA complexes, whereas the defect in ob/ob macrophages was reversed by treatment with eicosapentaenoic acid/BSA or by feeding ob/ob mice a fish oil diet rich in ω-3 FAs. There was also defective macrophage efferocytosis in atherosclerotic lesions of ob/ob;Ldlr mice and this was reversed by a fish oil-rich diet. CONCLUSIONS:: The findings suggest that in obesity and type 2 diabetes elevated levels of saturated FAs and/or decreased levels of ω-3 FAs contribute to decreased macrophage efferocytosis. Beneficial effects of fish oil diets in atherosclerotic cardiovascular disease may involve improvements in macrophage function related to reversal of defective efferocytosis and could be particularly important in type 2 diabetes and obesity.

KW - Atherosclerosis

KW - Efferocytosis

KW - Fatty acids

KW - Macrophages

KW - Mouse

UR - http://www.scopus.com/inward/record.url?scp=72949092179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72949092179&partnerID=8YFLogxK

U2 - 10.1161/CIRCRESAHA.109.199570

DO - 10.1161/CIRCRESAHA.109.199570

M3 - Article

C2 - 19834009

AN - SCOPUS:72949092179

VL - 105

SP - 1072

EP - 1082

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 11

ER -