A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha.
OBJECTIVE
Weight gain is associated with infiltration of fat by macrophages, suggesting that they are an important source of inflammation in obese adipose tissue. Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate.


RESULTS
Coculture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in the marked upregulation of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), and the downregulation of the antiinflammatory cytokine adiponectin. Such inflammatory changes are induced by the coculture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-alpha, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF-alpha is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, free fatty acids (FFAs) may be important adipocyte-derived mediators of inflammation in macrophages, because the production of TNF-alpha in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the coculture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice.


CONCLUSIONS
We postulate that a paracrine loop involving FFAs and TNF-alpha between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue.
Suganami
Takayoshi
T
Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Nishida
Junko
J
Ogawa
Yoshihiro
Y
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006984:Hypertrophy; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D024821:Metabolic Syndrome / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005230:Fatty Acids, Nonesterified; D014409:Tumor Necrosis Factor-alpha