Impact of dietary lipid intake on LR depends on composition: diets enriched in olive/fish oils increase, while high fat diets decrease hepatocyte proliferation after PH by causing steatosis and inflammation. We previously showed that overexpression of the NFқB inhibitory and hepatoprotective protein A20 improves FA metabolism. This culminates
in decreased oxidative stress and increased energy production, thereby improving mouse survival following severe liver ischemia/ reperfusion injury, and lethal radical hepatectomy. In contrast, partial loss of A20 (heterozygous (HT) mice) delays LR and increases lethality (42%) following PH, through impaired lipid metabolism and increased inflammation. In this study, we evaluated the impact of a fish oil (FO) diet on LR. A20 HT and wild type (WT) mice were Rucaparib fed 7% FO or soybean (SO) oil diets for 4 weeks prior BTK inhibitor in vivo to 2/3 PH. We noted significantly less proliferating (Ki67+) hepatocytes and heightened macrosteatosis (Oil Red O staining) correlating with increased lethality (>15% vs. 0%) in SO fed HT, as compared to WT mice, 48h after PH. Remarkably, FO feeding of HT
mice abrogated death post PH by improving hepatocyte proliferation and reducing steatosis. This benefit related to FO lowering higher Fatty Acid Synthase mRNA levels noted in SO fed HT mice, as compared to WT. This reduced de novo lipogenesis, as evidenced by lower levels of palmitic acid. In addition, increased fatty acid uptake observed in SO fed HT after surgery was normalized by FO diet, as demonstrated by reduced content of the essential fatty acids linoleic and alpha-linoleic. Finally, FO diet reduced proinflammatory arachidonic acid and increased anti-inflammatory eicosapentaenoic and docosahexaenoic fatty acids in livers of HT mice as compared to SO diet. This decreased liver inflammation after PH, as evaluated by mRNA levels of Serum Amyloid A1. WT mice faired similarly well, regardless of diet.
This is the first demonstration that dietary manipulation of lipid composition prior to PH restores hepatocyte proliferative ability, improving outcome in A20 HT mice. The clinical relevance of these findings is emphasized by recently described gene polymorphisms associated with A20′s decreased expression or function. We 上海皓元 propose that FO rich diets offer a safe and inexpensive means to overcome genetic predisposition in patients with unfavorable A20 polymorphisms, allowing for better outcomes following liver transplantation, mainly living donor liver transplantation. Disclosures: The following people have nothing to disclose: Cleide G. Da Silva, Peter Studer, Eva Csizmadia, Darlan C. Minussi, Kathleen Daniels, Christiane Ferran To improve outcomes of liver cell therapy, superior engraftment of transplanted cells and liver repopulation is critical. As hepatocyte transplantation in liver rapidly induces microcirculatory disturbances, e. g.