Gastrointestinal Therapeutics

Biography

Biography: Jude A Oben

Abstract

Background: The global prevalence of obesity-induced liver disease (non-alcoholic fatty liver disease, NAFLD) is rising. Suggested causes include a role for in utero influences of maternal obesity compounded by availability of energy dense foods throughout postnatal life. We investigated the role of maternal obesity in the context of an postnatal obesogenic diet in the trans-generational of obesity and mechanisms therein. \\\\\\\\\\\\\\\\r\\\\\\\\\\\\\\\\n\\\\\\\\\\\\\\\\r\\\\\\\\\\\\\\\\nMethods: Female C57BL/6J mice were fed a standard or an obesogenic diet, before and throughout pregnancy, and during lactation. Female offspring were weaned onto standard or an obesogenic diet at 3 weeks postpartum. Biochemical and histological indicators of dysmetabolism, NAFLD and fibrosis; analysis of pro-fibrotic pathways, liver innate immune cells were investigated at 3, 6 and 12 months. \\\\\\\\\\\\\\\\r\\\\\\\\\\\\\\\\n\\\\\\\\\\\\\\\\r\\\\\\\\\\\\\\\\nResults: Female offspring exposed to a post-weaning obesogenic diet (OffCon-OD) demonstrated evidence of liver injury exacerbated by prior exposure to maternal obesity (OffOb-OD) as demonstrated by ALT, hepatic triglycerides and hepatic expression of IL-6, TNF-α, TGF-β, ASMA and collagen (p < 0.01). Histological evidence of hepatosteatosis and a more robust NAFLD phenotype with hepatic fibrosis was observed at 12 months in OffOb-OD. A role for the innate immune system was indicated by increased Kupffer cell (KC) numbers with impaired phagocytic function and raised ROS synthesis (p < 0.01) together with reduced NK-T cells and raised IL-12 and IL-18. \\\\\\\\\\\\\\\\r\\\\\\\\\\\\\\\\n\\\\\\\\\\\\\\\\r\\\\\\\\\\\\\\\\nConclusions: Maternal obesity in the context of a post-natal hyper-calorific obesogenic diet aggressively programs offspring NAFLD associated with innate immune dysfunction, resulting in a comprehensive phenotype that accurately reflects the human disease. \\\\\\\\\\\\\\\\r\\\\\\\\\\\\\\\\n