1. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity
- Author
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Yoshikazu Tamori, Kensuke Egashira, Hajime Kanda, Sakan Maeda, Sanshiro Tateya, Sohei Kitazawa, Masato Kasuga, Ko Kotani, Riko Kitazawa, Hitoshi Miyachi, and Kenichi Hiasa
- Subjects
Male ,medicine.medical_specialty ,FGF21 ,Adipose tissue macrophages ,Mice, Obese ,Adipose tissue ,Mice, Transgenic ,White adipose tissue ,Carbohydrate metabolism ,Biology ,Mice ,Insulin resistance ,Internal medicine ,medicine ,Animals ,Humans ,Obesity ,RNA, Messenger ,Chemokine CCL2 ,Triglycerides ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,Macrophages ,Fatty liver ,3T3 Cells ,General Medicine ,medicine.disease ,Dietary Fats ,Fatty Liver ,Mice, Inbred C57BL ,Glucose ,Endocrinology ,Adipose Tissue ,Insulin Resistance ,Steatosis ,Research Article - 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.
- Published
- 2006