title: In vitro Modulation of the LPS-Induced Proinflammatory Profile of Hepatocytes and Macrophages- Approaches for Intervention in Obesity?
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.
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of LeicesterLeicester, UK; College of Nursing, University of RaparinRanya, Iraq.
authors.forename: Ramiar K
authors.initials: RK
authors.lastname: Kheder
authors.affiliation: Department of Sport, Health, and Exercise Science, University of Hull Hull, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hobkirk
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester Leicester, UK.
authors.forename: Cordula M
authors.initials: CM
authors.lastname: Stover
keywords: HepG2; J774; Vitamin D3; docosahexaenoic acid; lipopolysaccharide