title: Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy.
abstract: The aim of this study was to assess the effect of Ω3 fatty acids (Ω3FA) on fatty and lean liver in hepatic surgery.
  
  
  
  The global spread of energy-dense diets has led to an endemic rise in fatty liver disease and obesity. Besides metabolic pathologies, steatosis enhances hepatic sensitivity to ischemia reperfusion (I/R) and impedes liver regeneration (LR). Steatosis limits the application of liver surgery, still the main curative option for liver cancer. Ω3FA are known to reverse steatosis, but how these lipids affect key factors defining surgical outcomes-that is, I/R, LR, and liver malignancy-is less clear.
  
  
  
  We established a standardized mouse model of high fat diet (HFD)-induced steatosis followed by Ω3FA treatment and the subsequent assessment of Ω3FA effects on I/R, LR, and liver malignancy (n = 5/group), the latter through a syngeneic metastasis approach. Fatty liver outcomes were compared with lean liver to assess steatosis-independent effects. Nonparametric statistics were applied.
  
  
  
  Ω3FA reversed HFD-induced steatosis and markedly protected against I/R, improved LR, and prolonged survival of tumor-laden mice. Remarkably, these beneficial effects were also observed in lean liver, albeit at a smaller scale. Notably, mice with metastases in fatty versus lean livers were associated with improved survival.
  
  
  
  Ω3FA revealed multiple beneficial effects in fatty and lean livers in mice. The improvements in I/R injury, regenerative capacity, and oncological outcomes await confirmatory studies in humans.
authors: *Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland †Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland ‡Hepatology Unit, Department of Clinical Research, University Hospital Bern, Bern, Switzerland.
authors: Michael
authors: M
authors: Linecker
authors: Perparim
authors: P
authors: Limani
authors: Patryk
authors: P
authors: Kambakamba
authors: Philipp
authors: P
authors: Kron
authors: Christoph
authors: C
authors: Tschuor
authors: Nicolas
authors: N
authors: Calo
authors: Michelangelo
authors: M
authors: Foti
authors: Jean-François
authors: JF
authors: Dufour
authors: Rolf
authors: R
authors: Graf
authors: Bostjan
authors: B
authors: Humar
authors: Pierre-Alain
authors: PA
authors: Clavien
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000601:surgery*; D015427:Reperfusion Injury / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D015525:Fatty Acids, Omega-3