Two faces of PPARα/NFκB signaling pathway in inflammatory responses to adipocytes lipolysis in grass carp Ctenopharyngodon idella

Abstract Adipose tissue plays an important role in energy reservation, also be considered as vital immunological organ in animals. Adipocytes are the basic unit of adipose tissue, while little is known about the relationship between lipid metabolism and inflammatory response in fish adipocytes so far. In this study, forskolin was used to induce adipocyte lipolysis, and 5 μM forskolin and 30 μM forskolin both triggered lipolysis by increasing ATGL expression. Consequently, 30 μM Forskolin instead of 5 μM Forskolin induced the expression of NF-κB and its target pro-inflammatory cytokine genes including MCP-1, IL-6 and TNF-α. Further study found that low grade rate of lipolysis activated PPARα gene, and its inhibitory effect on the mRNA expression of NF-κB and its target genes inhibited the adipocyte inflammation. On the contrary, high grade rate of lipolysis increased the expression levels of NF-κB and its target genes, while their expression were attenuated by inhibition of reactive oxygen species (ROS) using α-tocopherol, suggesting that ROS generated due to the PPARα-mediated oxidation of released fatty acids from lipolysis may contribute to adipocyte inflammation. These results indicated that PPARα has dose effect in inflammatory responses to adipocyte lipolysis in grass carp. Taken together, grass carp adipocytes have immune activity. The inflammatory response is linked to the grade rate of adipocyte lipolysis in grass carp adipocytes, and excessive adipocyte lipolysis may promote a dynamic immune response in adipose tissue. This is the first study showing the regulatory effects of lipolysis on immune functions in fish adipocytes.