RRC ID 43307
著者 Toyoda T, Kamei Y, Kato H, Sugita S, Takeya M, Suganami T, Ogawa Y.
タイトル Effect of peroxisome proliferator-activated receptor-alpha ligands in the interaction between adipocytes and macrophages in obese adipose tissue.
ジャーナル Obesity (Silver Spring)
Abstract OBJECTIVE:This study was designed to examine the effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) ligands on the inflammatory changes induced by the interaction between adipocytes and macrophages in obese adipose tissue.
METHODS AND PROCEDURES:PPAR-alpha ligands (Wy-14,643 and fenofibrate) were added to 3T3-L1 adipocytes, RAW264 macrophages, or co-culture of 3T3-L1 adipocytes and RAW264 macrophages in vitro, and monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) mRNA expression and secretion were examined. PPAR-alpha ligands were administered to genetically obese ob/ob mice for 2 weeks. Moreover, the effect of PPAR-alpha ligands was also evaluated in the adipose tissue explants and peritoneal macrophages obtained from PPAR-alpha-deficient mice.
RESULTS:In the co-culture of 3T3-L1 adipocytes and RAW264 macrophages, PPAR-alpha ligands reduced MCP-1 and TNF-alpha mRNA expression and secretion in vitro relative to vehicle-treated group. The anti-inflammatory effect of Wy-14,643 was observed in adipocytes treated with macrophage-conditioned media or mouse recombinant TNF-alpha and in macrophages treated with adipocyte-conditioned media or palmitate. Systemic administration of PPAR-alpha ligands inhibited the inflammatory changes in adipose tissue from ob/ob mice. Wy-14,643 also exerted an anti-inflammatory effect in the adipose tissue explants but not in peritoneal macrophages obtained from PPAR-alpha-deficient mice.
DISCUSSION:This study provides evidence for the anti-inflammatory effect of PPAR-alpha ligands in the interaction between adipocytes and macrophages in obese adipose tissue, thereby improving the dysregulation of adipocytokine production and obesity-related metabolic syndrome.
巻・号 16(6)
ページ 1199-207
公開日 2008-6-1
DOI 10.1038/oby.2008.62
PII oby200862
PMID 18356826
MeSH 3T3-L1 Cells Adipocytes / drug effects* Adipocytes / metabolism Adipocytes / pathology Animals Anti-Inflammatory Agents / pharmacology Cell Communication / drug effects* Cell Line Chemokine CCL2 / metabolism Coculture Techniques Disease Models, Animal Fenofibrate / pharmacology* Ligands Macrophages / drug effects* Macrophages / metabolism Macrophages / pathology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Obese Obesity / metabolism* Obesity / pathology PPAR alpha / genetics PPAR alpha / metabolism* Peritoneal Cavity / pathology Pyrimidines / pharmacology* RNA, Messenger / metabolism Tumor Necrosis Factor-alpha / metabolism
IF 3.742
引用数 25
WOS 分野 NUTRITION & DIETETICS ENDOCRINOLOGY & METABOLISM
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)