Received: 3 December 2017 | Accepted: 12 February 2018 DOI: 10.1002/jcp.26537 ORIGINAL RESEARCH ARTICLE Omega-3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells Md Soriful Islam 1,2 | Clara Castellucci 3 | Rosamaria Fiorini 4 | Stefania Greco 1 | Riccardo Gagliardi 5 | Alessandro Zannotti 1 | Stefano R. Giannubilo 6 | Andrea Ciavattini 6 | Natale G. Frega 7 | Deborah Pacetti 7 | Pasquapina Ciarmela 1,8 1 Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy 2 Biotechnology and Microbiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh 3 Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy 4 Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy 5 Eureka srl - Lab Division, R&D Department, Chiaravalle (AN), Italy 6 Department of Clinical Science, Università Politecnica delle Marche, Ancona, Italy 7 Department of Agricultural, Food and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy 8 Department of Information Engineering, Università Politecnica delle , Marche, Ancona, Italy Correspondence Pasquapina Ciarmela, PhD, Faculty of Medicine, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, via Tronto 10/a, 60020 Ancona, Italy. Email: p.ciarmela@univpm.it Deborah Pacetti, PhD, Department of Agricultural, Food and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy. Email: d.pacetti@univpm.it Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega-3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin β1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid-crystalline phase, but EPA- and DHA-treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega-3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option. KEYWORDS ABCG1 and ABCA1, lipid profile, mechanical signaling, omega-3 fatty acids, uterine leiomyoma 1 | INTRODUCTION Uterine leiomyomas (fibroids or myomas), originating from myometrial smooth muscle cells of the uterus, are the most common benign tumors of fertile women (Bulun, 2013; Protic et al., 2016). Uterine leiomyomas affect about 77% of women of reproductive-age and approximately 25% of reproductive-age women bear clinically apparent tumors (Buttram & Reiter, 1981; Cramer & Patel, 1990). The incidence and severity of symptoms typically depend on the size, number, and location of the fibroids (Buttram & Reiter, 1981). The common symptoms associated with uterine leiomyomas are irregular and excessive menstrual bleeding, which often causes anaemia, pain in Md Soriful Islam, Clara Castellucci, and Rosamaria Fiorini contributed equally to this work. J Cell Physiol. 2018;1–14. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc. | 1