The Eicosapentaenoic Acid Metabolite 15-Deoxy-δ12,14-Prostaglandin J3 Increases Adiponectin Secretion by Adipocytes Partly via a PPARγ-Dependent Mechanism

Abstract

The intake of ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA) increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ12,14-PGJ3 (15d-PGJ3), a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ)-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s) for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation.

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

“…Thus, we cannot exclude that the competition between EPA and AA was more effi cient in the production of other prostaglandin families. Moreover, we had no access to potentially highly important local changes such as the formation of 15d-PGJ3 in adipose tissue ( 61 ). A further limitation may come from the use of currently available surrogate parameters (stable prostaglandin degradation products) that only partially refl ect the actual utilization of EPA by COX enzymes ( 62 ).…”

Docosahexaenoic Acid

“…PPARs are activated by noncovalent binding of ligands which include n-3 LCPUFAs and various lipid mediators. DHA can induce and activate PPARs [53] and upregulate a number of PPAR target genes [54] , which may be at least partly responsible for the ability of DHA to lower fasting plasma triglyceride concentrations [55] , to increase insulin sensitivity [56] and to reduce inflammation [57] .…”

Data Uncertainty in Virtual Network Embedding: Robust Optimization and Protection Levels

“…Lipid mediators produced from EPA and DHA can also bind and regulate PPAR-γ, this being an important mechanism by which n-3 fatty acids affect inflammatory processes. For example, the EPA derivatives prostaglandin D 3 and 15-deoxy-prostaglandin D 3 activate PPAR-γ in adipocytes, a process linked to the induction of the anti-inflammatory adipokine adiponectin (91). Thus, activation of PPAR-γ may itself be one of the anti-inflammatory mechanisms of action of n-3 fatty acids and this may also link to the inhibition of NF-κB activation described above.…”