Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance*

By Nozomu Kamei, K. Tobe, R. Suzuki, M. Ohsugi, Taku Watanabe, N. Kubota, Norie Ohtsuka-Kowatari, Katsuyoshi Kumagai, K. Sakamoto, Masatoshi Kobayashi and 14 more. Journal of Biological Chemistry, 2006

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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-α 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.

Subfields: Cardiology and Cardiovascular Medicine, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/554eb1e8021af04498fbe7cb8ce6230db889a208

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Citations in the corpus

Macrophage-mediated inflammation in metabolic disease (2011, background): “Although transgenic expression of CCL2 in adipose tissue is sufficient to enhance macrophage recruitment and potentiate obesity-induced insulin resistanc”
Macrophages, immunity, and metabolic disease. (2014, background): “, 2006), and overexpression of adipocyte MCP-1was sufficient to induce adipose inflammation and insulin resistance in lean mice (Kamei et al., 2006).”
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training (2013, neutral): “For instance, there is some suggestion that deletion of MCP1 or its receptor, CCR2, confers protection against adipose tissue macrophage accumulation, insulin resistance, and atherosclerosis during high fat feeding (329, 471, 682) whereas adipocyte-specific overexpression of MCP1 promotes macrophage”
Cellular and Molecular Players in Adipose Tissue Inflammation in the Development of Obesity-induced Insulin Resistance (2013, neutral): “Probably the only two examples of AT-specific mouse models are the AT-specific MCP-1 transgenic mice [50,51] and the Treg-specific PPARγ knockout mice [89].”
Inflammation and insulin resistance (2008, background): “pression of Mcp1 in adipose tissue can enhance macrophage infiltration and cause insulin resistance [48,49].”
Adipocytes as regulators of energy balance and glucose homeostasis (2006, background): “, and overexpression of MCP-1 has the opposite effec”
A crucial role for adipose tissue p53 in the regulation of insulin resistance (2009, background): “It has been reported that increased secretion of proinflammatory cytokines by adipose tissue exacerbates insulin resistance in people with metabolic disorder”
Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease (2014, background): “Over-expression of CCL2/MCP-1 in adipose tissue increases macrophage recruitment and worsens the metabolic phenotype [71,72], whereas a deficiency of CCL2/MCP-1 or its receptor CCR2 reduces pro-inflammatory macrophages accumulation in adipose tissue and provides protection from insulin resistance as”
Molecular Inflammation: Underpinnings of Aging and Age-related Diseases (2008, background): “Overexpression of Mcp1 (a chemokine) increases macrophage infiltration, inflammation, and insulin resistance (Kamei et al., 2006).”