Effect of Peroxisome Proliferator-activated Receptor-α Ligands in the Interaction Between Adipocytes and Macrophages in Obese Adipose Tissue
Article first published online: 6 SEP 2012
2008 North American Association for the Study of Obesity (NAASO)
Volume 16, Issue 6, pages 1199–1207, June 2008
How to Cite
Toyoda, T., Kamei, Y., Kato, H., Sugita, S., Takeya, M., Suganami, T. and Ogawa, Y. (2008), Effect of Peroxisome Proliferator-activated Receptor-α Ligands in the Interaction Between Adipocytes and Macrophages in Obese Adipose Tissue. Obesity, 16: 1199–1207. doi: 10.1038/oby.2008.62
- Issue published online: 6 SEP 2012
- Article first published online: 6 SEP 2012
- Received June 16, 2007; Accepted September 11, 2007
Objective: This study was designed to examine the effect of peroxisome proliferator-activated receptor-α (PPAR-α) ligands on the inflammatory changes induced by the interaction between adipocytes and macrophages in obese adipose tissue.
Methods and Procedures: PPAR-α 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-α (TNF-α) mRNA expression and secretion were examined. PPAR-α ligands were administered to genetically obese ob/ob mice for 2 weeks. Moreover, the effect of PPAR-α ligands was also evaluated in the adipose tissue explants and peritoneal macrophages obtained from PPAR-α-deficient mice.
Results: In the co-culture of 3T3-L1 adipocytes and RAW264 macrophages, PPAR-α ligands reduced MCP-1 and TNF-α 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-α and in macrophages treated with adipocyte-conditioned media or palmitate. Systemic administration of PPAR-α 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-α-deficient mice.
Discussion: This study provides evidence for the anti-inflammatory effect of PPAR-α ligands in the interaction between adipocytes and macrophages in obese adipose tissue, thereby improving the dysregulation of adipocytokine production and obesity-related metabolic syndrome.