Fish Oil Derived Omega 3 Fatty Acids Suppress Adipose NLRP3 Inflammasome Signaling in Human Obesity

• Published in: Journal of the Endocrine Society Vol. 3; no. 3; pp. 504 - 515
• Main Authors: Lee, Kailey Roberts, Midgette, Yasmeen, Shah, Rachana
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.03.2019; Oxford University Press
• Subjects: Adipocytes; Clinical s; Clinical trials; Fish oils; Gene expression; Obesity; Polyunsaturated fatty acids; nutrition; adipose; inflammation; obesity
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/js.2018-00220

Abstract Context The NRLP3 inflammasome is a multiprotein danger-sensing complex that serves as a critical link between obesity-related adipose inflammation and insulin resistance and has been shown in animal models to be inhibited by fish oil-derived long chain omega-3 polyunsaturated fatty acids (n-3 PUFA). Objective We conducted a clinical trial and in vitro experiments to test our hypothesis that n-3 PUFA suppress NLRP3 inflammasome in human obesity through downregulation of inflammasome gene expression in adipocytes and macrophages. Design Placebo-controlled clinical trial and in vitro coculture experiments with primary human adipocytes (from biopsy specimens) and human THP-1 monocyte-derived macrophages treated with eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) vs vehicle control. Setting General community, research laboratory. Patients and Other Participants Obese (body mass index ≥ 30 kg/m2), nondiabetic males and females age 18 to 50. N = 25. Interventions Clinical trial: Eight-week treatment with 4 g Lovaza (EPA and DHA) or placebo. Cells culture: EPA and/or DHA at 100 µg/mL or vehicle control in culture medium. Main Outcome Measures Adipose tissue or adipocyte/macrophage mRNA expression of IL-1β and IL-18 and circulating IL-18 levels. Results Treatment of obese human subjects with fish oil supplements reduced expression of adipose inflammatory genes including inflammasome-associated IL-18 and IL-1β and circulating IL-18 levels. Both EPA and DHA reduced inflammasome gene expression in obese human adipose and human adipocyte and macrophages. Conclusions N-3 PUFA reduce NLRP3 inflammasome in human adipose through downregulation of gene expression in adipocytes and monocytes/macrophages and has potential as nutritional therapeutic agent in prevention of obesity-related inflammation.