The accumulation of fat in the liver is a hidden health danger. Initially, it has no detrimental effect; but as the buildup grows, inflammation and irreversible scarring of the liver occur, leading to chronic liver disease. Researchers are still trying to solve the puzzle of how this process unfolds.
Gastrointestinal pathologist Dr. Shawn Winer and his twin brother TGHRI Scientist Dr. Dan Winer
have been working to uncover the factors that control fatty liver disease development and progression. They recently used an experimental model of fatty liver disease to show that high-fat diets increase the levels of a proteins characteristic of a type 1 interferon response in the liver.
This increase drives the accumulation of specific immune cells (CD8+ T cells) that cause an imbalance in blood sugar levels—a common symptom of non-alcoholic fatty liver disease. Furthermore, when the Winer brothers tested certain compounds that interfered with the function of type 1 interferon in an experimental model of fatty liver disease, many of the negative symptoms were reduced.
These experimental results were further supported by the team’s clinical study, performed in collaboration with Saint Louis University Hospital, Washington University School of Medicine and Mid-American Transplant Services. The results of the study showed that increases in CD8+ T cells and type 1 interferon responses in the liver correlated with the clinical signs of non-alcoholic fatty liver disease as wells as worsened blood sugar levels.
This ground-breaking study highlights the important role that interferon plays in the development and progression of non-alcoholic fatty liver disease. The results also reveal a new therapeutic strategy: development of drugs capable of targeting type 1 interferon and related pathways may help combat obesity-related liver disease.
This work was supported by the Canadian Institutes of Health Research, the Canadian Diabetes Association, the J.P. Bickell Foundation, the Ontario Ministry of Research, Innovation and Science Early Researcher Award and the Toronto General & Western Hospital Foundation. D Winer holds a Tier 2 Canada Research Chair in Immunometabolism.
Ghazarian M, Revelo XS, Nøhr MK, Luck H, Zeng K, Lei H, Tsai S, Schroer SA, Park YJ, Chng MHY, Shen L, D’Angelo JA, Horton P, Chapman WC, Brockmeier D, Woo M, Engleman EG, Adeyi O, Hirano N, Jin T, Gehring A, Winer S, Winer D. Type I interferon responses drive intrahepatic T cells to promote metabolic syndrome. Sci Immunol. 2017 Apr 21. doi.org/10.1126/sciimmunol.aai7616