AUTHOR=Kheder Ramiar K. , Hobkirk James , Stover Cordula M. 

TITLE=In vitro Modulation of the LPS-Induced Proinflammatory Profile of Hepatocytes and Macrophages- Approaches for Intervention in Obesity?

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=4

YEAR=2016

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2016.00061

DOI=10.3389/fcell.2016.00061

ISSN=2296-634X

ABSTRACT=<p>Low grade endotoxemia is a feature of obesity which is linked to development of steatohepatitis in non-alcoholic fatty liver disease. In this study, macrophages (J774) and hepatocytes (HepG2) were stimulated with lipopolysaccharide (LPS) from <italic>E. coli</italic> 0111: B4 and analyzed for modulation of this response when preconditioned or stimulated subsequent to LPS, with different doses of Vitamin D<sub>3</sub> or docosahexaenoic acid (DHA) over a time period of 1 and 5 days. Pro-inflammatory TNFα and pro-fibrotic TGFβ released into the supernatants were measured by ELISA; qPCR was performed for Srebp-1c and PPARα mRNA (genes for products involved in fatty acid synthesis and catabolism, respectively). Vitamin D<sub>3</sub> and DHA exerted a consistent, dose dependent anti-inflammatory effect, and increased PPARα relative to Srebp-1c in both cell types. By contrast, addition of free fatty acids (FFA, oleic acid/palmitic acid 2:1) caused aggravation of LPS-induced inflammatory reaction and an increase of Srebp-1c relative to PPARα. Our results argue in favor of dietary supplementation of Vitamin D<sub>3</sub> or DHA (and avoidance of monounsaturated/saturated fatty acids) to alleviate development of fatty liver disease.</p>