Pericardial adipose tissue (PAT) as a cell model to assess patient responsiveness to docosahexaenoic acid (DHA) and eicopentaenoic acid (EPA)

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Abstract Background The abundance of epicardial (EAT) and pericardial adipose tissue (PAT) is associated with several cardiac risk factors and a higher carotid intima-media thickness, with a potential contributory role to the development of atherosclerosis and coronary artery disease (CAD). Under conditions promoting obesity, both epicardial and pericardial adipose tissue undergo a metabolic shift, acquiring an inflammatory and pro-atherogenic phenotype. Addressing dysmetabolism and inflammation associated with EAT and PAT are a promising and innovative therapeutic approach for preventing coronary atherosclerosis. Recent data have highlighted a noteworthy association between the abundance of adipose tissue n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as their ratio to the omega-6 FA arachidonic acid (AA), with a lower risk of myocardial infarction. Purpose To develop an efficient method for isolation of adipocytes from human PAT and evaluation of adipocyte response to DHA and EPA. Methods PAT samples were collected from 9 CAD patients, undergoing coronary artery bypass graft surgery and immediately processed before to assess more than 50 experimental conditions. Isolated adipocytes were morphologically and molecularly characterized. Cell responsiveness was evaluated by cell exposure to inflammatory stimuli, with or without variable amounts of DHA, EPA, or AA assessing a spectrum of gene expressions and pro-inflammatory functional activities. Results Pure cultures of pericardial adipocytes exhibited prolonged viability (beyond 72 hours). and retained responsiveness to pro-inflammatory and lipolytic stimuli, while also showing the capacity to activate the insulin signalling pathway. Cell exposure to DHA or EPA resulted in a downregulation of messenger (m)RNA expression for monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and metalloproteinase (MMP)-9 (p<0.05) and in upregulation of uncoupling protein-(UCP)-1, UCP-2 and peroxisome proliferator-activated receptor (PPAR)γ (p< 0.05) (Figure 1). In line with mRNA expression, a significant reduction in both cytokines and MMP-9 protein release was observed (p<0.05) (Figure 2). These effects paralleled a significant incorporation of DHA and EPA into total cell lipids (p<0.05). Functionally, the cell supernatant from DHA- or EPA-conditioned cells displayed diminished ability to attract monocytes in chemotaxis assays. AA exhibited no such activities. Conclusion(s) In a novel cellular model of isolated and cultured adipocytes from PAT, DHA and EPA attenuated the inflammatory and dysmetabolic characteristics of this cardiac adipose tissue.

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