Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

Abstract

Objective: The aim of this study was to assess the effect of V3 fatty acids (V3FA) on fatty and lean liver in hepatic surgery. Background: 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. V3FA 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. Methods: We established a standardized mouse model of high fat diet (HFD)-induced steatosis followed by V3FA treatment and the subsequent assessment of V3FA effects on I/R, LR, and liver malignancy (n ¼ 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. Results: V3FA 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. Conclusions: V3FA 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.

Increased dietary fatty acids determine the fatty-acid profiles of human pancreatic cancer cells and their carrier’s plasma, pancreas and liver

“…When we transplanted HPAF-2 human pancreatic cancer cells in the pancreas of athymic mice, we found that liver metastasis was increased by n6PUFA-enriched diet and decreased by n3PUFAenriched diet [16]. In addition, dietary FAs also regulated liver metastasis of colorectal cancer [32,33]. In the present study, diet-derived unsaturated FAs induced an increase of the same FAs in the liver.…”

Exercise Improves Outcomes of Surgery on Fatty Liver in Mice

“…We established above findings in a mouse model of obesityassociated NAFLD, 9 where exercise could replicate the known benefits of physical activity, including the ameliorations in body weight, steatosis, hyperinsulinemia, and glucose tolerance. 2 Our observations are hence based on a valid experimental set up and underscore the importance of exercise for liver health.…”

“…Six weeks of feeding a HFD designed to mimic Western diet induced obesity and NAFLD without inflammation/fibrosis in mice. 9 Mean body-and liver weight increased by 11.9 g (AE2.4) and 0.8 g (AE0.2), respectively ( Fig. 1B), accompanied by a marked elevation in hepatic lipid content (Fig.…”

“…1,2,4,6 Fatty liver also displays a markedly reduced ability to tolerate ischemic injury or to regenerate after tissue loss. 9 The impact of exercise on acute liver stress however is unknown. We therefore established a mouse model of diet-induced steatosis, where we were able to replicate the known metabolic benefits of exercising.…”

Effects of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on postoperative complications for patients with Crohn’s disease: a cohort study

“…The postoperative rehabilitation improvement mediated by ω-3 PUFAs may be due to regulation of the arachidonic acid pathway and control of the release of prostaglandins, thromboxanes, leukotrienes and other molecules, which reduces the levels of in ammatory molecules such as IL-6, IL-8, and TNF- [35][36][37] ; regulation of sterol regulatory element binding protein (SREBP-1), protein acylation reactions and calcium ion release, which maintains cell membrane integrity, stability, and uidity, thus reducing the production and release of cytokines and ameliorating, the postoperative in ammatory response 38 ; alteration of the phospholipid composition and function of T-cell membranes, which enhances the function of antigenpresenting cells and the cytotoxicity of natural killer cells and regulates the function of dendritic cells to affect immune function 39 ; and regulation of the intestinal ora and their metabolites, such as short chain fatty acids 40 .…”