(PO25-51-22) 8-Hydroxyeicosapentaenoic Acid Reduces Adipogenesis and Inflammation in 3T3-L1 Adipocytes

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Presenting Author(s)

Yujiao Zu, PhD
– Research Assistant Professor, Texas Tech University, LUBBOCK, Texas, United States

Co-Author(s)

Naima Moustaid-Moussa, Ph.D.
– Professor, Texas Tech University, Lubbock, Texas, United States
MM

Mark Mikhael
– Texas Tech University
SS

Shane Scoggin, BS
– Texas Tech University, Lubbock, Texas, United States
AP

Anandita Pal
– University of North Carolina at Chapel Hill
SS

Saame R. Shaikh, PhD
– Associate Professor, UNC Chapel Hill, Chapel Hill, North Carolina, United States

Disclosure(s):

Yujiao Zu, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Obesity is a complex disease and a chronic low-grade inflammatory state, which contributes to metabolic dysfunctions. Eicosapentaenoic acid (EPA), an n-3 fatty acid in fish oil, exerts anti-obesity and anti-inflammatory effects. Our previous study indicated that EPA lowered fat mass in obese female mice, potentially through increased biosynthesis of 8-hydroxyeicosapentaenoic acid (HEPE), an EPA-derived metabolite. Therefore, the objective of this study was to elucidate mechanisms underlying 8-HEPE effects on adipogenesis and inflammation using cultured 3T3-L1 cells. We hypothesized that 8-HEPE is more effective than EPA in reducing lipid accumulation and inflammatory genes in vitro.

Methods: Murine 3T3-L1 adipocytes were cultured and differentiated with 5μM EPA, 18-HEPE, 8-HEPE, or control. Differentiated adipocytes were fixed and stained with Oil-Red-O solution and lipid content measured spectrophotometrically. To determine anti-inflammatory effects, 3T3-L1 pre- and differentiated cells were treated as above with or without lipopolysaccharide (LPS). Medium and cells were collected to measure interleukin-6 (IL-6) levels and genes involved in adipogenesis and inflammation. Results were analyzed by one-way ANOVA followed by a Tukey post-hoc test (GraphPad Prism).

Results: 3T3-L1 cells differentiated with 8-HEPE had lower lipid content than control (p < 0.01). Consistently, 8-HEPE treated cells expressed a lower level of fatty acid synthesis gene, like acetyl-CoA carboxylase and fatty acid synthase than control (p=0.059 and p=0.042). And 8-HEPE exhibited promising anti-inflammatory effects by downregulating the IL-6 cytokine level in both LPS stimulated pre- and differentiated 3T3-L1 cells (p < 0.05). LPS-stimulated differentiated cells treated with 8-HEPE expressed a lower level of the inflammatory gene, IL-6 (p=0.017), and a trend toward a higher level of the anti-inflammatory gene, arginase 1 (p=0.067), than LPS control.

Conclusions: Our findings indicate that the 8-HEPE has potent antiadipogenic and anti-inflammatory effects in vitro, and merit further investigations in vivo to determine whether EPA’s effects are mediated by its downstream metabolite 8-HEPE. Our findings further demonstrate the importance of studying the role of EPA-derived metabolites in obesity and inflammation.

Funding Sources: None