PMID- 16988077 OWN - NLM STAT- MEDLINE DCOM- 20061030 LR - 20080121 IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 14 IP - 8 DP - 2006 Aug TI - Mesenteric adipose tissue-derived monocyte chemoattractant protein-1 plays a crucial role in adipose tissue macrophage migration and activation in obese mice. PG - 1353-62 AB - OBJECTIVE: To determine whether chemokines, which play a pivotal role in monocyte/macrophage trafficking, modulate macrophage infiltration into and activation in the adipose tissues. RESEARCH METHODS AND PROCEDURES: Various types of adipose tissue were isolated from different fat depots (e.g., mesenteric, epididymal, renal, and subcutaneous adipose tissues) from obese mice fed a high-fat diet and from non-obese controls fed a standard diet. The isolated tissues were cultured for 24, 48, and 72 hours. The level of monocyte chemoattractant protein-1 (MCP-1) expression and the amount of protein released were measured by reverse transcriptase-polymerase chain reaction or enzyme-linked immunosorbent assay, respectively. Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring the concentrations of nitric oxide and tumor necrosis factor alpha. RESULTS: The level of MCP-1 mRNA expression, protein content, and the amount of protein released significantly increased in the adipose tissues from the obese mice compared with those from the non-obese mice. The mesenteric adipose tissue produced the highest levels of MCP-1 protein among the four different fat depots. Mesenteric adipose tissue-conditioned medium induced the highest degree of macrophage migration and strongly induced macrophages to produce proinflammatory mediators such as nitric oxide and tumor necrosis factor alpha. The neutralization of MCP-1 in the adipose tissue-conditioned medium significantly inhibited the migration and activation of macrophages. DISCUSSION: Our findings suggest that MCP-1 plays a crucial role in adipose tissue inflammatory response by activating and inducing the infiltration of macrophages into adipose tissues. MCP-1 may be closely associated with visceral obesity-related complications and, thus, may be a useful therapeutic target for modulating visceral obesity-related diseases. FAU - Yu, Rina AU - Yu R AD - Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Korea. rinayu@ulsan.ac.kr FAU - Kim, Chu-Sook AU - Kim CS FAU - Kwon, Byung-Se AU - Kwon BS FAU - Kawada, Teruo AU - Kawada T LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Antibodies) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD68 antigen, human) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Culture Media, Conditioned) RN - 0 (Dietary Fats) RN - 0 (RNA, Messenger) SB - IM MH - Adipose Tissue/*metabolism MH - Animals MH - Antibodies/pharmacology MH - Antigens, CD/genetics/metabolism MH - Antigens, Differentiation, Myelomonocytic/genetics/metabolism MH - Cell Line MH - Chemokine CCL2/*genetics/immunology/metabolism MH - Chemotaxis/drug effects/physiology MH - Culture Media, Conditioned/pharmacology MH - Dietary Fats/administration & dosage MH - Enzyme-Linked Immunosorbent Assay MH - Gene Expression MH - Macrophage Activation/drug effects/physiology MH - Macrophages/cytology/drug effects/*physiology MH - Male MH - Mesentery/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Obesity/etiology/*physiopathology MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tissue Culture Techniques EDAT- 2006/09/22 09:00 MHDA- 2006/10/31 09:00 CRDT- 2006/09/22 09:00 PHST- 2006/09/22 09:00 [pubmed] PHST- 2006/10/31 09:00 [medline] PHST- 2006/09/22 09:00 [entrez] AID - 14/8/1353 [pii] AID - 10.1038/oby.2006.153 [doi] PST - ppublish SO - Obesity (Silver Spring). 2006 Aug;14(8):1353-62. doi: 10.1038/oby.2006.153.