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 2

Tissue distribution of MCP-1 mRNA and plasma concentration of MCP-1 in obese mice.

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Tissue distribution of MCP-1 mRNA a...
(A) Total RNA was extracted from the indicated tissues of 8-week-old db/db or db/+m mice and subjected to Northern blot analysis with a probe specific for mouse MCP-1 mRNA. WAT, white adipose tissue; BAT, brown adipose tissue. (B) Plasma concentration of MCP-1 in 11-week-old db/+m and db/db mice. Data are mean ± SEM (db/+m, n = 8; db/db, n = 11). *P < 0.05 versus db/+m. (C) Total RNA, extracted from the indicated tissues of 18-week-old C57BL/6J mice fed either a high-fat diet (HFD) or normal chow for 12 weeks, was subjected to Northern blot analysis with a probe specific for MCP-1 mRNA. (D) Plasma concentration of MCP-1 in 18-week-old C57BL/6J mice fed normal chow or the high-fat diet for 12 weeks. Data are mean ± SEM (normal chow, n = 11; high-fat diet, n = 9). *P < 0.05 versus normal chow. (E) Total RNA (15 μg), extracted from the SVF and adipocyte fraction (Adipo) of epididymal fat tissue from 11-week-old db/db mice or 18-week-old C57BL/6J mice fed a high-fat diet for 12 weeks, was subjected to Northern blot analysis with a probe specific for MCP-1 mRNA. The intensity of the band corresponding to MCP-1 mRNA in each fraction was quantitated and expressed relative to the value for the SVF of mice fed a high-fat diet. Data are mean ± SEM of values from 3 independent experiments (n = 3).