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Fish‐oils Increase BAMBI Expression to Protect Against Fibrotic Activity in LPS Stimulated Hepatic Tissue
Author(s) -
Schaller Megan L.,
Harris Matthew P.,
Kamm Dakota,
Witt Kenneth A.,
Sandoval Karin E.,
Wooten Joshua S.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.887.4
Subject(s) - fish oil , fibrosis , medicine , cd14 , endocrinology , inflammation , chemistry , tlr4 , adipose tissue , hepatic fibrosis , stimulation , biology , fish <actinopterygii> , receptor , fishery
Non‐alcoholic steatohepatitis (NASH), defined as excess hepatic lipid and chronic inflammation, provides an environment prone for the development of hepatic fibrosis. Recent evidence suggests that the antifibrotic protein BAMBI (BMP‐Activin membrane bound inhibitor) is downregulated in the presence of inflammation, and may be central to the development of fibrosis. Diets rich in omega‐3 (ω‐3) fatty acids are known to provide anti‐inflammatory effects; however, the effects of ω‐3 fatty acids on hepatic fibrosis are not well‐established. PURPOSE To determine the effects of fish‐oils on the hepatic fibrosis signaling cascade, following 32‐weeks of high‐fat feeding in a LPS‐induced model of NASH. METHODS Male C57BL/6 mice were randomly assigned to one of four diets for 32 weeks (n=9/group): low‐fat lard based (LFL, 10% kcal fat), low‐fat fish‐oil based (LFFO, 10% kcal fat), high‐fat lard based (HFL, 41% kcal fat), or high‐fat fish‐oil based (HFFO, 41% kcal fat). Following in situ LPS stimulation, liver mRNA expression of CD14, TLR4, MyD88, BAMBI, and TGF‐β1 was quantified using quantitative RT‐PCR. Differences between diets were identified using a one‐way ANOVA with statistical significance set at p<0.05. RESULTS Following LPS stimulation, CD14 was increased 2.5 fold (p=0.020) in HFFO when compared to HFL. Despite the increase in CD14, TLR4 showed no difference between groups. In contrast, MyD88 was 2.8 fold greater (p<0.001) in HFL compared to HFFO. In comparison to untreated tissue, BAMBI was 1.7 fold (p=0.017) higher in the HFFO LPS‐stimulated tissue, which best explained the 1‐fold (p=0.004) lower expression of TGF‐β1 in HFFO when compared to HFL post‐LPS stimulation. CONCLUSION Despite the increase in extracellular LPS signaling receptor CD14, the consumption of fish‐oils produced a protective intracellular response as observed by an increase in BAMBI and decrease in TGF‐β1. These results suggest that a diet high in ω‐3 fatty acids may protect against the development of hepatic fibrosis. Support or Funding Information Supported by NIH R21NS090282‐01