Ramiar K. Kheder
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.
Dr James Hobkirk J.Hobkirk@hull.ac.uk
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. 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||Oct 27, 2022|
|Journal||Frontiers in cell and developmental biology|
|Peer Reviewed||Peer Reviewed|
|Keywords||Vitamin D₃; Docosahexaenoic acid; HepG2; J774; Lipopolysaccharide|
|Additional Information||Copy of article first published in: Frontiers in cell and developmental biology, 2016, v.4|
Publisher Licence URL
© 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.