Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance Export

@article{Kamei:2006p957, abstract = {Adipose tissue expression and circulating concentrations of monocyte chemoattractant protein-1 (MCP-1) correlate positively with adiposity. To ascertain the roles of MCP-1 overexpression in adipose, we generated transgenic mice by utilizing the adipocyte P2 (aP2) promoter (aP2-MCP-1 mice). These mice had higher plasma MCP-1 concentrations and increased macrophage accumulation in adipose tissues, as confirmed by immunochemical, flow cytometric, and gene expression analyses. Tumor necrosis factor-alpha and interleukin-6 mRNA levels in white adipose tissue and plasma non-esterified fatty acid levels were increased in transgenic mice. aP2-MCP-1 mice showed insulin resistance, suggesting that inflammatory changes in adipose tissues may be involved in the development of insulin resistance. Insulin resistance in aP2-MCP-1 mice was confirmed by hyperinsulinemic euglycemic clamp studies showing that transgenic mice had lower rates of glucose disappearance and higher endogenous glucose production than wild-type mice. Consistent with this, insulin-induced phosphorylations of Akt were significantly decreased in both skeletal muscles and livers of aP2-MCP-1 mice. MCP-1 pretreatment of isolated skeletal muscle blunted insulin-stimulated glucose uptake, which was partially restored by treatment with the MEK inhibitor U0126, suggesting that circulating MCP-1 may contribute to insulin resistance in aP2-MCP-1 mice. We concluded that both paracrine and endocrine effects of MCP-1 may contribute to the development of insulin resistance in aP2-MCP-1 mice.}, author = {Kamei, Nozomu and Tobe, Kazuyuki and Suzuki, Ryo and Ohsugi, Mitsuru and Watanabe, Taku and Kubota, Naoto and Kowatari, Norie O. and Kumagai, Katsuyoshi and Sakamoto, Kentaro and Kobayashi, Masatoshi and Yamauchi, Toshimasa and Ueki, Kohjiro and Oishi, Yumiko and Nishimura, Satoshi and Manabe, Ichiro and Hashimoto, Haruo and Ohnishi, Yasuyuki and Ogata, Hitomi and Tokuyama, Kumpei and Tsunoda, Masaki and Ide, Tomohiro and Murakami, Koji and Nagai, Ryozo and Kadowaki, Takashi}, citeulike-article-id = {3046164}, citeulike-linkout-0 = {http://www.jbc.org/cgi/content/full/281/36/26602}, citeulike-linkout-1 = {http://dx.doi.org/10.1074/jbc.M601284200}, doi = {10.1074/jbc.M601284200}, journal = {J Biol Chem}, keywords = {acid-binding, acids, adipose, animals, antimetabolites, body, c57bl, ccl2, cells, chemokine, clamp, cultured, deoxyglucose, diet, dietary, factor-alpha, fats, fatty, file-import-08-07-27, genetics, glucose, inbred, insulin, interleukin-6, macrophages, mice, myoblasts, necrosis, nonesterified, obese, promoter, proteins, regions, resistance, signal, skeletal, technique, tissue, transduction, transgenic, tumor, weight}, local-url = {file://localhost/Users/ken/Documents/Papers/2006/Kamei/J\%20Biol\%20Chem\%202006\%20Kamei.pdf}, month = {Sep}, number = {36}, pages = {26602--14}, posted-at = {2008-07-27 14:45:51}, priority = {2}, title = {Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance}, url = {http://dx.doi.org/10.1074/jbc.M601284200}, volume = {281}, year = {2006} }

TY - JOUR ID - Kamei:2006p957 L3 - citeulike-article-id:3046164 N2 - Adipose tissue expression and circulating concentrations of monocyte chemoattractant protein-1 (MCP-1) correlate positively with adiposity. To ascertain the roles of MCP-1 overexpression in adipose, we generated transgenic mice by utilizing the adipocyte P2 (aP2) promoter (aP2-MCP-1 mice). These mice had higher plasma MCP-1 concentrations and increased macrophage accumulation in adipose tissues, as confirmed by immunochemical, flow cytometric, and gene expression analyses. Tumor necrosis factor-alpha and interleukin-6 mRNA levels in white adipose tissue and plasma non-esterified fatty acid levels were increased in transgenic mice. aP2-MCP-1 mice showed insulin resistance, suggesting that inflammatory changes in adipose tissues may be involved in the development of insulin resistance. Insulin resistance in aP2-MCP-1 mice was confirmed by hyperinsulinemic euglycemic clamp studies showing that transgenic mice had lower rates of glucose disappearance and higher endogenous glucose production than wild-type mice. Consistent with this, insulin-induced phosphorylations of Akt were significantly decreased in both skeletal muscles and livers of aP2-MCP-1 mice. MCP-1 pretreatment of isolated skeletal muscle blunted insulin-stimulated glucose uptake, which was partially restored by treatment with the MEK inhibitor U0126, suggesting that circulating MCP-1 may contribute to insulin resistance in aP2-MCP-1 mice. We concluded that both paracrine and endocrine effects of MCP-1 may contribute to the development of insulin resistance in aP2-MCP-1 mice. IS - 36 JF - J Biol Chem EP - 14 TI - Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance VL - 281 SP - 26602 KW - acid-binding KW - acids KW - adipose KW - animals KW - antimetabolites KW - body KW - c57bl KW - ccl2 KW - cells KW - chemokine KW - clamp KW - cultured KW - deoxyglucose KW - diet KW - dietary KW - factor-alpha KW - fats KW - fatty KW - file-import-08-07-27 KW - genetics KW - glucose KW - inbred KW - insulin KW - interleukin-6 KW - macrophages KW - mice KW - myoblasts KW - necrosis KW - nonesterified KW - obese KW - promoter KW - proteins KW - regions KW - resistance KW - signal KW - skeletal KW - technique KW - tissue KW - transduction KW - transgenic KW - tumor KW - weight AU - Kamei, Nozomu AU - Tobe, Kazuyuki AU - Suzuki, Ryo AU - Ohsugi, Mitsuru AU - Watanabe, Taku AU - Kubota, Naoto AU - Kowatari, Norie AU - Kumagai, Katsuyoshi AU - Sakamoto, Kentaro AU - Kobayashi, Masatoshi AU - Yamauchi, Toshimasa AU - Ueki, Kohjiro AU - Oishi, Yumiko AU - Nishimura, Satoshi AU - Manabe, Ichiro AU - Hashimoto, Haruo AU - Ohnishi, Yasuyuki AU - Ogata, Hitomi AU - Tokuyama, Kumpei AU - Tsunoda, Masaki AU - Ide, Tomohiro AU - Murakami, Koji AU - Nagai, Ryozo AU - Kadowaki, Takashi PY - 2006/Sep// UR - http://dx.doi.org/10.1074/jbc.M601284200 ER -