Effect of Peroxisome Proliferator‐activated Receptor‐α Ligands in the Interaction Between Adipocytes and Macrophages in Obese Adipose Tissue

Abstract

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.

Telmisartan increases lipoprotein lipase expression via peroxisome proliferator-activated receptor-alpha in HepG2 cells

“…PPARa expression has been reported in adipose tissue (33,34), and preclinical data suggest a role of PPARa in body weight control, supporting the potential use of PPARa agonists in the treatment of obesity (35). A previous study demonstrated that PPARa ligand strongly inhibits atherosclerosis and attenuates macrophage-related inflammation in atherosclerotic foam cells (36); this was explained by the finding that PPARa activation decreases obesity-related adipose tissue inflammation (33,37). Additional studies are needed to explore the effect of telmisartan-induced PPARa activation on adipocytokines and inflammation in adipose tissue.…”

Modulatory Effect of Fenofibrate on Endothelial Production of Neutrophil Chemokines IL-8 and ENA-78

“…In addition, evidence of fibrate antiinflammatory effects continues to emerge [20][21][22][23][24][25][26]. While Fig.…”

Proline oxidase–adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation

“…46,47 Interestingly, the activation of PPARa inhibits the expression of several genes involved in proinflammatory response in adipocytes including TNFa. 48,49 On the basis of this evidence, it is likely that the marked increase of TNFa detected in the AT of ATGL KO mice is also the consequence of impaired ATGL-mediated PPARa expression.…”