Maternal obesity programs offspring nonalcoholic fatty liver disease by innate immune dysfunction in mice

• DOI: 10.1002/hep.26248
• Publication Date: 2013-01-12T12:29:40Z
• Authors: Angelina Mouralid...; Junpei Soeda; Clara Visconti-Pu...; Anne-Maj Samuelsson; Joaquim Pombo; Xanthi Maragkoudaki; Adil Butt; Ruma Saraswati; Marco Novelli; Guiseppe Fusai; Lucilla Poston; Paul D. Taylor; Jude A. Oben
• Keywords: Kupffer cell

Abstract The global prevalence of obesity-induced liver disease (nonalcoholic fatty disease; NAFLD) is rising. Suggested causes include a role for in utero influences maternal obesity compounded by the availability energy-dense foods throughout postnatal life. Using physiologically relevant model, we investigated innate immune system injury induced followed obesogenic diet. Female C57BL/6J mice were fed standard or diet before and pregnancy during lactation. offspring weaned onto at 3 weeks postpartum. Biochemical histological indicators dysmetabolism, NAFLD fibrosis, analysis profibrotic pathways, cells, reactive oxygen species (ROS) 3, 6, 12 months. exposed to postweaning (OffCon-OD) demonstrated evidence injury, which was exacerbated previous exposure (OffOb-OD), as raised alanine aminotransferase, hepatic triglycerides, expression interleukin (IL)-6, tumor necrosis factor alpha, transforming growth beta, alpha smooth muscle actin, collagen ( P < 0.01). Histological hepatosteatosis more-robust phenotype with fibrosis observed months OffOb-OD. A indicated increased Kupffer cell numbers impaired phagocytic function ROS synthesis 0.01), together reduced natural killer T cells (IL)-12 IL-18. Conclusion: Maternal context hypercalorific aggressively programs associated dysfunction, resulting comprehensive that accurately reflects human disease. (HEPATOLOGY 2013)