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Given its long progression and rising incidence, dietary prevention is positioned as an actionable strategy. The study examines how diets enriched with ω3 and ω6 polyunsaturated fatty acids influence disease progression. 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Subbaiah 3, Cecilia Leal 4, Sam Grimaldo 3, Francisco M. Ortuno 6, Faraz Bishehsari 7 and Paul J. Grippo 3,8, *  \nReceived: 24 October 2024  \nRevised: 17 December 2024  \nAccepted: 20 December 2024  \nPublished: 31 December 2024  \nCitation: Torres, C.; Mancinelli, G.; Chen, J.-W.E.; Cordoba-Chacon, J.; Pins, D.; Saeed, S.; McKinney, R.; Castellanos, K.; Orsi, G.; Singhal, M.; et al. Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT. Nutrients 2025, 17, 150. [https://](https://)[ ](https://)[doi.org/10.3390/nu17010150](doi.org/10.3390/nu17010150)  \n[Copyright:](Copyright:) © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, 18071 Granada, Spain  \n2 Instituto de Investigacion Biosanitaria ibs.GRANADA, 18012 Granada, Spain  \n3 Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; [gms891@gmail.com](gms891@gmail.com) (G.M.); [sarah.saeed@advocatehealth.com](sarah.saeed@advocatehealth.com) (S.S.); [mckinney@uic.edu](mckinney@uic.edu) (R.M.); [akshp64@gmail.com](akshp64@gmail.com) (A.P.)  \n4 Department of Materials Science & Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; [emily.chen@lilly.com](emily.chen@lilly.com) (J.-W.E.C.)  \n5 Hospital San Raffaelle, 20132 Milan, Italy  \n6 Department of Computer Architecture and Computer Technology, University of Granada,  \n18071 Granada, Spain  \n7 Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA  \n8 Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois Chicago, 840 S. Wood Street, CSB 708, Chicago, IL 60612, USA  \n* Correspondence: [ctp@ugr.es](ctp@ugr.es) (C.T.); [pgrippo@uic.edu](pgrippo@uic.edu) (P.J.G.)  \nAbstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10–20 years), prevention strategies represent an effective means to improve outcomes. Oneof the risk factors for many cancers and for pancreatic cancer in particular is diet. Hence, our objective is to understand how a diet rich in ω3 and ω6 polyunsaturated fatty acids affects the progression of this disease. Methods: We investigated polyunsaturated fatty acid (PUFA) effects on disease progression employing both in vitro (PDAC cell lines) and in vivo (EL-Kras and KC mice) approaches. Also, we gathered data from the National Health and Nutrition Examination Survey (NHANES) and the National Cancer Institute (NCI) from 1999 to 2017 for a retrospective observational study. Results: The consumption of PUFAs in a patient population correlates with increased PDAC incidence, particularly when the ω3 intake increases to a lesser extent than ω6 . Our data demonstrate dietary PUFAs can be incorporated into plasma membrane lipids affecting PI3K/AKT signaling and support the emergence of membrane-targeted therapies. Moreover, we show that the phospholipid composition of a lipid nanoparticle (LNP) can impact the","cbCaiusk3VipR8T0","https://ap.wps.com/l/cbCaiusk3VipR8T0","pdf",8421443,25,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What disease and prevention focus does the study address?\",\"answer\":\"The study focuses on pancreatic ductal adenocarcinoma (PDAC) and the potential of dietary prevention strategies to improve outcomes in a cancer with very poor prognosis.\"},{\"question\":\"How were the effects of polyunsaturated fatty acids (PUFAs) investigated?\",\"answer\":\"PUFA effects were tested using in vitro PDAC cell lines and in vivo EL-Kras and KC mice, and complemented by retrospective observational data from NHANES and NCI from 1999 to 2017.\"},{\"question\":\"What signaling pathway and membrane-related mechanisms are highlighted?\",\"answer\":\"The findings link dietary PUFAs incorporated into plasma membrane lipids to PI3K/AKT signaling, and indicate that phospholipid composition of a lipid nanoparticle can affect membrane integrity and cell viability after administration.\"}]","Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT | PDF",1790038700,63]