title: Replacement of Dietary Saturated Fat by PUFA-Rich Pumpkin Seed Oil Attenuates Non-Alcoholic Fatty Liver Disease and Atherosclerosis Development, with Additional Health Effects of Virgin over Refined Oil.
abstract: OBJECTIVE
  As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore, besides potential health effects conferred by the type of fatty acids in a vegetable oil, other minor components (e.g. phytochemicals) may also have health benefits. Here, we investigated the potential long-term health effects of isocaloric substitution of dietary fat (i.e. partial replacement of saturated by unsaturated fats), as well as putative additional effects of phytochemicals present in unrefined (virgin) oil on development of non-alcoholic fatty liver disease (NAFLD) and associated atherosclerosis. For this, we used pumpkin seed oil, because it is high in unsaturated fatty acids and a rich source of phytochemicals.
  
  
  METHODS
  ApoE*3Leiden mice were fed a Western-type diet (CON) containing cocoa butter (15% w/w) and cholesterol (1% w/w) for 20 weeks to induce risk factors and disease endpoints. In separate groups, cocoa butter was replaced by refined (REF) or virgin (VIR) pumpkin seed oil (comparable in fatty acid composition, but different in phytochemical content).
  
  
  RESULTS
  Both oils improved dyslipidaemia, with decreased (V)LDL-cholesterol and triglyceride levels in comparison with CON, and additional cholesterol-lowering effects of VIR over REF. While REF did not affect plasma inflammatory markers, VIR reduced circulating serum amyloid A and soluble vascular adhesion molecule-1. NAFLD and atherosclerosis development was modestly reduced in REF, and VIR strongly decreased liver steatosis and inflammation as well as atherosclerotic lesion area and severity.
  
  
  CONCLUSIONS
  Overall, we show that an isocaloric switch from a diet rich in saturated fat to a diet rich in unsaturated fat can attenuate NAFLD and atherosclerosis development. Phytochemical-rich virgin pumpkin seed oil exerts additional anti-inflammatory effects resulting in more pronounced health effects.
authors.affiliation: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, the Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Martine C
authors.initials: MC
authors.lastname: Morrison
authors.affiliation: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, the Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Mulder
authors.affiliation: Bunge Ltd., White Plains, New York, United States of America.
authors.forename: P Mark
authors.initials: PM
authors.lastname: Stavro
authors.affiliation: Department of Biochemistry and Biotechnology, Rovira iVirgili University, Tarragona, Spain; Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Reus, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Suárez
authors.affiliation: Department of Biochemistry and Biotechnology, Rovira iVirgili University, Tarragona, Spain; Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Arola-Arnal
authors.affiliation: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, the Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van Duyvenvoorde
authors.affiliation: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, the Netherlands.
authors.forename: Teake
authors.initials: T
authors.lastname: Kooistra
authors.affiliation: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, the Netherlands.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Wielinga
authors.affiliation: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, the Netherlands; Department of Human and Animal Physiology, Wageningen University, Wageningen, the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001808:Blood Vessels / Q000473:pathology; D002784:Cholesterol; D028464:Cucurbita / Q000737:chemistry*; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated / Q000627:therapeutic use*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D005227:Fatty Acids / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008055:Lipids / Q000097:blood; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D064209:Phytochemicals / Q000032:analysis; D010938:Plant Oils / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D008055:Lipids; D064209:Phytochemicals; D010938:Plant Oils; C052387:cocoa butter; D002784:Cholesterol