Details

Autor(en) / Beteiligte

• Eritja, Nuria
• Arjó, Gemma
• Santacana, Maria
• Gatius, Sònia
• Ramírez-Núñez, Omar
• Arcal, Laura
• Serrano, José C.E.
• Pamplona, Reinald
• Dolcet, Xavi
• Piñol, Carme
• Christou, Paul
• Matias-Guiu, Xavier
• Portero-Otin, Manuel

Titel

Oral intake of genetically engineered high-carotenoid corn ameliorates hepatomegaly and hepatic steatosis in PTEN haploinsufficient mice

Ist Teil von

• Biochimica et biophysica acta, 2016-04, Vol.1862 (4), p.526-535

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2016

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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. •HCAR diet reduces severity of NAFLD symptoms linked to PTEN haploinsufficiency.•HCAR diet increases hepatic RA-levels.•HCAR diet diminishes SREBP-1C expression by inducing AMPKα in PTEN+/− mice livers.•AMPKα signaling is activated by RA-dependent pathways.•Carotenoids may serve as a preventive diet intervention to predisposed NAFLD cases.