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

@article{Kanda:2006p952, 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.}, author = {Kanda, Hajime and Tateya, Sanshiro and Tamori, Yoshikazu and Kotani, Ko and Hiasa, Ken I. and Kitazawa, Riko and Kitazawa, Sohei and Miyachi, Hitoshi and Maeda, Sakan and Egashira, Kensuke and Kasuga, Masato}, citeulike-article-id = {3046184}, citeulike-linkout-0 = {http://www.jci.org/articles/view/JCI26498}, citeulike-linkout-1 = {http://dx.doi.org/10.1172/JCI26498}, doi = {10.1172/JCI26498}, journal = {J Clin Invest}, keywords = {3t3, adipose, analysis, animals, array, c57bl, ccl2, cells, chemokine, dietary, fats, fatty, file-import-08-07-27, glucose, humans, inbred, insulin, knockout, liver, macrophages, male, messenger, mice, obese, obesity, oligonucleotide, resistance, rna, sequence, tissue, transgenic, triglycerides}, local-url = {file://localhost/Users/ken/Documents/Papers/2006/Kanda/J\%20Clin\%20Invest\%202006\%20Kanda.pdf}, month = {Jun}, number = {6}, pages = {1494--505}, posted-at = {2008-07-27 14:46:01}, priority = {2}, title = {MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity}, url = {http://dx.doi.org/10.1172/JCI26498}, volume = {116}, year = {2006} }

TY - JOUR ID - Kanda:2006p952 L3 - citeulike-article-id:3046184 N2 - 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. IS - 6 JF - J Clin Invest EP - 505 TI - MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity VL - 116 SP - 1494 KW - 3t3 KW - adipose KW - analysis KW - animals KW - array KW - c57bl KW - ccl2 KW - cells KW - chemokine KW - dietary KW - fats KW - fatty KW - file-import-08-07-27 KW - glucose KW - humans KW - inbred KW - insulin KW - knockout KW - liver KW - macrophages KW - male KW - messenger KW - mice KW - obese KW - obesity KW - oligonucleotide KW - resistance KW - rna KW - sequence KW - tissue KW - transgenic KW - triglycerides AU - Kanda, Hajime AU - Tateya, Sanshiro AU - Tamori, Yoshikazu AU - Kotani, Ko AU - Hiasa, Ken AU - Kitazawa, Riko AU - Kitazawa, Sohei AU - Miyachi, Hitoshi AU - Maeda, Sakan AU - Egashira, Kensuke AU - Kasuga, Masato PY - 2006/Jun// UR - http://dx.doi.org/10.1172/JCI26498 ER -