Abstract 396: Role of Monocyte Chemotactic Protein-1 in Obesity Involves a Newly Discovered Transcription Factor MCPIP
Monocyte chemotactic protein-1 (MCP) that is well known to play a major role in the development of cardiovascular diseases, was recently reported to be involved also in obesity. We recently discovered that MCP-1 treatment of human monocytes induces a novel CCCH zinc finger transcription factor designated MCP-induced protein (MCPIP). In the present study we report that in the white adipose tissue of high fat diet fed mice, MCPIP was induced when body mass and fasting glucose level were elevated, beginning at about 8 weeks on the diet. Six MCPIP-induced novel genes, with no previously known function, ltv, lzp, creld2, ufm1, cdh12 and cdh19, were induced in the white adipose tissue, starting at three months of high fat feeding; the increases in fasting glucose level, MCPIP transcript level and the transcript levels of the novel genes showed further progressive increases during the 5 months on the high fat diet. Similar molecular events were also observed during differentiation of NIH 3T3 -L1 cells into adipocytes in culture in the presence of dexamethasone and insulin. Under these conditions MCP-1 production was induced reaching a peak level at 24hr. MCPIP transcript level showed marked increase within 1 hr and reached a maximum at 2 days. ufm1, lzp, and creld2 reached maximal levels at 4 hr, whereas ltv reached maximal level in 1–2 days, and cdh12 and cdh19 reached maximal levels in one day. Involvement of MCPIP in the differentiation process was indicated by the finding that transfection of 3T3 cells with MCPIP expression plasmid caused differentiation of these cells into adipocytes under non-inducing conditions in the absence of dexamethasone and insulin. This differentiation was accompanied by induction of the six novel MCPIP-induced genes. Knockdown of MCPIP with specific siRNA suppressed differentiation of 3T3 cells into adipocytes and induction of the six MCPIP-induced genes. These results indicate a role for MCP-1 in adipogenesis and that this role is mediated via the newly discovered transcription factor MCPIP.