PMID- 13129912 OWN - NLM STAT- MEDLINE DCOM- 20040203 LR - 20210206 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 278 IP - 47 DP - 2003 Nov 21 TI - Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. PG - 46654-60 AB - Obesity is currently considered as an epidemic in the western world, and it represents a major risk factor for life-threatening diseases such as heart attack, stroke, diabetes, and cancer. Taking advantage of DNA microarray technology, we tried to identify the molecules explaining the relationship between obesity and vascular disorders, comparing mRNA expression of about 12,000 genes in white adipose tissue between normal, high fat diet-induced obesity (DIO) and d-Trp34 neuropeptide Y-induced obesity in mice. Expression of monocyte chemoattractant protein-1 (MCP-1) mRNA displayed a 7.2-fold increase in obese mice as compared with normal mice, leading to substantially elevated MCP-1 protein levels in adipocytes. MCP-1 levels in plasma were also increased in DIO mice, and a strong correlation between plasma MCP-1 levels and body weight was identified. We also showed that elevated MCP-1 protein levels in plasma increased the CD11b-positive monocyte/macrophage population in DIO mice. Furthermore, infusion of MCP-1 into lean mice increased the CD11b-positive monocyte population without inducing changes in body weight. Given the importance of MCP-1 in activation of monocytes and subsequent atherosclerotic development, these results suggest a novel role of adiposity in the development of vascular disorders. FAU - Takahashi, Kazuhiko AU - Takahashi K AD - Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Tsukuba, Ibaraki 300-2611, Japan. FAU - Mizuarai, Shinji AU - Mizuarai S FAU - Araki, Hiromitsu AU - Araki H FAU - Mashiko, Satoshi AU - Mashiko S FAU - Ishihara, Akane AU - Ishihara A FAU - Kanatani, Akio AU - Kanatani A FAU - Itadani, Hiraku AU - Itadani H FAU - Kotani, Hidehito AU - Kotani H LA - eng PT - Journal Article DEP - 20030916 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CD11b Antigen) RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) SB - IM MH - Adipose Tissue/chemistry/metabolism MH - Animals MH - Arteriosclerosis/etiology MH - CD11b Antigen/*analysis MH - Chemokine CCL2/blood/genetics/*physiology MH - Gene Expression Profiling MH - Macrophage Activation MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/*cytology/immunology MH - Obesity/*blood/complications MH - RNA, Messenger/analysis EDAT- 2003/09/18 05:00 MHDA- 2004/02/05 05:00 CRDT- 2003/09/18 05:00 PHST- 2003/09/18 05:00 [pubmed] PHST- 2004/02/05 05:00 [medline] PHST- 2003/09/18 05:00 [entrez] AID - S0021-9258(20)75947-8 [pii] AID - 10.1074/jbc.M309895200 [doi] PST - ppublish SO - J Biol Chem. 2003 Nov 21;278(47):46654-60. doi: 10.1074/jbc.M309895200. Epub 2003 Sep 16.