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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.


Ramiar K. Kheder

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Dr James Hobkirk
Lecturer in Physiology & Pathophysiology & Honorary Medical Scientist

Cordula M. Stover


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.


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.

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
Keywords Vitamin D₃; Docosahexaenoic acid; HepG2; J774; Lipopolysaccharide
Public URL
Publisher URL
Additional Information Copy of article first published in: Frontiers in cell and developmental biology, 2016, v.4


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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.

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