Mesenteric adipose tissue-derived monocyte chemoattractant protein-1 plays a crucial role in adipose tissue macrophage migration and activation in obese mice.
OBJECTIVE
To determine whether chemokines, which play a pivotal role in monocyte/macrophage trafficking, modulate macrophage infiltration into and activation in the adipose tissues.


METHODS
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.


CONCLUSIONS
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.
Yu
Rina
R
Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Korea. rinayu@ulsan.ac.kr
Kim
Chu-Sook
CS
Kwon
Byung-Se
BS
Kawada
Teruo
T
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008643:Mesentery / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046509:Tissue Culture Techniques; D000097382:CD68 Molecule
D000906:Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D004041:Dietary Fats; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C491768:Ccl2 protein, mouse