Generation of new hepatocyte-like in vitro models better resembling human lipid metabolism

Publication date: Available online 11 February 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Camilla Pramfalk, Tomas Jakobsson, Cristy R.C. Verzijl, Mirko E. Minniti, Clara Obensa, Federico Ripamonti, Maria Olin, Matteo Pedrelli, Mats Eriksson, Paolo PariniAbstractIn contrast to human hepatocytes in vivo, which solely express acyl-coenzyme A:cholesterol acyltransferase (ACAT) 2, both ACAT1 and ACAT2 (encoded by SOAT1 and SOAT2) are expressed in primary human hepatocytes and in human hepatoma cell lines. Here, we aimed to create hepatocyte-like cells expressing the ACAT2, but not the ACAT1, protein to generate a model that – at least in this regard – resembles the human condition in vivo and to assess the effects on lipid metabolism. Using the Clustered Regularly Interspaced Short Palindromic Repeats technology, we knocked out SOAT1 in HepG2 and Huh7.5 cells. The wild type and SOAT2-only-cells were cultured with fetal bovine or human serum and the effects on lipoprotein and lipid metabolism were studied. In SOAT2-only-HepG2 cells, increased levels of cholesterol, triglycerides, apolipoprotein B and lipoprotein(a) in the cell media were detected; this was likely dependent of the increased expression of key genes involved in lipid metabolism (e.g. MTP, APOB, HMGCR, LDLR, ACACA, and DGAT2). Opposite effects were observed in SOAT2-only-Huh7.5 cells. Our study shows that the expression of SOAT1 in hepatocyte-like cells contribu...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research