In vitro modulation of the LPS-induced proinflammatory profile of hepatocytes and macrophages-approaches for intervention in obesity?

Kheder, Ramiar K.; Hobkirk, James; Stover, Cordula M.

doi:10.3389/fcell.2016.00061

In vitro modulation of the LPS-induced proinflammatory profile of hepatocytes and macrophages-approaches for intervention in obesity?

Kheder, Ramiar K.; Hobkirk, James; Stover, Cordula M.

Authors

Ramiar K. Kheder

Dr James Hobkirk J.Hobkirk@hull.ac.uk
Lecturer in Physiology & Pathophysiology & Honorary Medical Scientist

Cordula M. Stover

Abstract

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 E. coli 0111: B4 and analyzed for modulation of this response when preconditioned or stimulated subsequent to LPS, with different doses of Vitamin D₃ 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 D3 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 D₃ or DHA (and avoidance of monounsaturated/saturated fatty acids) to alleviate development of fatty liver disease.

Citation

Kheder, R. K., Hobkirk, J., & Stover, C. M. (2016). In vitro modulation of the LPS-induced proinflammatory profile of hepatocytes and macrophages-approaches for intervention in obesity?. Frontiers in Cell and Developmental Biology, 4(JUN), Article 61. https://doi.org/10.3389/fcell.2016.00061

Journal Article Type	Article
Acceptance Date	Jun 7, 2016
Online Publication Date	Jun 22, 2016
Publication Date	Jun 22, 2016
Deposit Date	Aug 30, 2016
Publicly Available Date	Aug 30, 2016
Journal	Frontiers in cell and developmental biology
Electronic ISSN	2296-634X
Publisher	Frontiers Media
Peer Reviewed	Peer Reviewed
Volume	4
Issue	JUN
Article Number	61
DOI	https://doi.org/10.3389/fcell.2016.00061
Keywords	Vitamin D₃; Docosahexaenoic acid; HepG2; J774; Lipopolysaccharide
Public URL	https://hull-repository.worktribe.com/output/442664
Publisher URL	http://journal.frontiersin.org/article/10.3389/fcell.2016.00061/full
Additional Information	Copy of article first published in: Frontiers in cell and developmental biology, 2016, v.4
Contract Date	Aug 30, 2016

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Copyright Statement
© 2016 Kheder, Hobkirk and Stover. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.