title: Oral intake of genetically engineered high-carotenoid corn ameliorates hepatomegaly and hepatic steatosis in PTEN haploinsufficient mice.
abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Here we show that a mouse model of haploinsufficiency in the lipid and protein phosphatase and tensin homolog protein (PTEN(+/-)) exhibits hepatomegaly, increased liver lipogenic gene expression (SREBP-1C and PPARγ) and hepatic lesions analogous to human NAFLD. The livers of PTEN(+/-) mice also contained lower levels of retinoic acid (RA) than normal, similarly to human NAFLD patients. The RA signaling pathway thus offers a novel therapeutic target for the treatment of NAFLD although the impact of nutrition in this context is unclear. We therefore fed PTEN(+/-) mice for 36weeks a diet containing genetically engineered high-carotenoid corn (HCAR) to investigate its potential beneficial effects on the hepatic symptoms of NAFLD. The HCAR diet reduced hepatomegaly and promoted the repartitioning of fatty acids in the liver, away from triacylglycerol storage. At the molecular level, the HCAR diet clearly reduced lipogenic gene expression, boosted catabolism, and increased hepatic RA levels. These results set the stage for human trials to evaluate the use of high-carotenoid foods for the reduction or prevention of steatosis in NAFLD.
authors.affiliation: Oncologic Pathology Group, Dept. de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain. Electronic address: neritja@irblleida.cat.
authors.forename: Nuria
authors.initials: N
authors.lastname: Eritja
authors.affiliation: Departament de Medicina, Universitat de Lleida-Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Arjó
authors.affiliation: Oncologic Pathology Group, Dept. de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Santacana
authors.affiliation: Oncologic Pathology Group, Dept. de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Gatius
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLleida, Av. Rovira Roure 80, 25198 Lleida, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Ramírez-Núñez
authors.affiliation: Departament de Medicina, Universitat de Lleida-Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Arcal
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLleida, Av. Rovira Roure 80, 25198 Lleida, Spain.
authors.forename: José C E
authors.initials: JCE
authors.lastname: Serrano
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLleida, Av. Rovira Roure 80, 25198 Lleida, Spain.
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.affiliation: Oncologic Pathology Group, Dept. de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
authors.forename: Xavi
authors.initials: X
authors.lastname: Dolcet
authors.affiliation: Departament de Medicina, Universitat de Lleida-Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Piñol
authors.affiliation: Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida-Agrotecnio Center, Lleida, Spain; Institució Catalana de Reserca i Estudis Avanc¸ats, Passeig Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: Paul
authors.initials: P
authors.lastname: Christou
authors.affiliation: Oncologic Pathology Group, Dept. de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLleida, Av. Rovira Roure 80, 25198 Lleida, Spain. Electronic address: manuel.portero@mex.udl.cat.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otin
mesh_terms: D000821:Animal Feed; D000818:Animals; D002338:Carotenoids / Q000494:pharmacology*; D005260:Female; D030841:Food, Genetically Modified; D057895:Haploinsufficiency; D006529:Hepatomegaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008817:Mice, Mutant Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D003313:Zea mays
chemical_list: D047495:PPAR gamma; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D002338:Carotenoids; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Genetically engineered high-carotenoid corn; Non-alcoholic fatty liver disease (NAFLD); PTEN; Retinoic acid