LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL

Lipids in Health and Disease

Research

Naoyuki Iso-O¹  Nobukazu Ishizaka²  Kazuhiko Koike³  Kyoji Moriya⁴  Makoto Kurano⁵  Kazuhisa Tsukamoto⁶  Masumi Hara⁷ 

[1]Department of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 108-8639, Tokyo, Japan

[2]Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 113-8655, Tokyo, Japan

[3]Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 113-8655, Tokyo, Japan

[4]Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 113-8655, Tokyo, Japan

[5]Department of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 113-8655, Tokyo, Japan

[6]Department of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 113-8655, Tokyo, Japan

[7]Department of Metabolism, Diabetes and Nephrology, Preparatory Office for Aizu Medical Center, Fukushima Medical University, 965-8555, Fukushima, Japan

[8]Fourth Department of Internal Medicine, Mizonokuchi Hospital, Teikyo University School of Medicine, 213-8507, Kanagawa, Japan

关键词: Spheroid HepG2 cells;    LXR agonist;    Apolipoprotein E;    ApoE rich HDL;    VLDL;   

DOI  :  10.1186/1476-511X-10-134

 received in 2011-07-08, accepted in 2011-08-05,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe physiological regulation of hepatic apoE gene has not been clarified, although the expression of apoE in adipocytes and macrophages has been known to be regulated by LXR.Methods and ResultsWe investigated the effect of TO901317, a LXR agonist, on hepatic apoE production utilizing HepG2 cells cultured in spheroid form, known to be more differentiated than HepG2 cells in monolayer culture. Spheroid HepG2 cells were prepared in alginate-beads. The secretions of albumin, apoE and apoA-I from spheroid HepG2 cells were significantly increased compared to those from monolayer HepG2 cells, and these increases were accompanied by increased mRNA levels of apoE and apoA-I. Several nuclear receptors including LXRα also became abundant in nuclear fractions in spheroid HepG2 cells. Treatment with TO901317 significantly increased apoE protein secretion from spheroid HepG2 cells, which was also associated with the increased expression of apoE mRNA. Separation of the media with FPLC revealed that the production of apoE-rich large HDL particles were enhanced even at low concentration of TO901317, and at higher concentration of TO901317, production of VLDL particles increased as well.ConclusionsLXR activation enhanced the expression of hepatic apoE, together with the alteration of lipoprotein particles produced from the differentiated hepatocyte-derived cells. HepG2 spheroids might serve as a good model of well-differentiated human hepatocytes for future investigations of hepatic lipid metabolism.

【 授权许可】

Unknown   
© Kurano et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.