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

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

    Research output: Contribution to journalArticlepeer-review

    1666 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1494-1505
    Number of pages12
    JournalJournal of Clinical Investigation
    Volume116
    Issue number6
    DOIs
    Publication statusPublished - Jun 1 2006

    All Science Journal Classification (ASJC) codes

    • Medicine(all)

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