MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity
Hajime Kanda, … , Kensuke Egashira, Masato Kasuga
Hajime Kanda, … , Kensuke Egashira, Masato Kasuga
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1494-1505. https://doi.org/10.1172/JCI26498.
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Research Article Metabolism

MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity

Abstract

Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein–1 (MCP-1) mRNA in adipose tissue and the plasma concentration of MCP-1 were increased both in genetically obese diabetic (db/db) mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to express an MCP-1 transgene in adipose tissue under the control of the aP2 gene promoter exhibited insulin resistance, macrophage infiltration into adipose tissue, and increased hepatic triglyceride content. Furthermore, insulin resistance, hepatic steatosis, and macrophage accumulation in adipose tissue induced by a high-fat diet were reduced extensively in MCP-1 homozygous KO mice compared with WT animals. Finally, acute expression of a dominant-negative mutant of MCP-1 ameliorated insulin resistance in db/db mice and in WT mice fed a high-fat diet. These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice.

Authors

Hajime Kanda, Sanshiro Tateya, Yoshikazu Tamori, Ko Kotani, Ken-ichi Hiasa, Riko Kitazawa, Sohei Kitazawa, Hitoshi Miyachi, Sakan Maeda, Kensuke Egashira, Masato Kasuga

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Figure 7

Effects of expression of the MCP-1 mutant 7ND on insulin sensitivity in obese mice.

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Effects of expression of the MCP-1 mutant 7ND on insulin sensitivity in ...
(A) Insulin tolerance test in db/db mice determined insulin sensitivity 21 days after transfection of 8-week-old animals with the 7ND vector (n = 10) or the corresponding empty plasmid as a control (Con, n = 6). (B) Insulin (left) and glucose (right) tolerance tests performed 21 days after transfection of 8-week-old db/+m mice with the 7ND vector (n = 8) or the corresponding empty plasmid (n = 7). (C) Insulin (left) and glucose (right) tolerance tests performed 21 days after transfection of 30-week-old C57BL/6J mice fed a high-fat diet since 6 weeks of age with either the 7ND expression vector or the corresponding empty plasmid. Data are mean ± SEM (insulin tolerance test, n = 4; glucose tolerance test, n = 5 [7ND], 7 [empty vector]). (D) Hyperinsulinemic-euglycemic clamp analysis of db/db mice performed 21 days after transfection of 8-week-old animals with the 7ND vector (n = 4) or the corresponding empty plasmid (n = 5). Data are mean ± SEM. (E) Appearance of the liver (left) and hepatic triglyceride content (n = 4, right) in db/db mice 21 days after injection of 8-week-old animals with the 7ND expression plasmid or the corresponding empty vector. *P < 0.05, **P < 0.01 versus mice injected with the empty vector.