Abstract P435: Probiotic Supplements Could Prevent Diet-induced Mitochondrial Dysfunction In The Liver Hepatocytes Of Apolipoprotein-e Knockout Mice

Abstract

A poor diet can modify the intestinal microbiota, known as gut dysbiosis, which causes hepatocyte mitochondrial dysfunction through the release of endotoxins in the portal vein. Mitochondrial dysfunction in the liver leads to non-alcoholic fatty liver disease (NAFLD). Epidemiological evidence shows that most deaths from NAFLD are related to cardiovascular diseases (CVD) demonstrated by impaired vasodilatation as well as increased arterial stiffness, calcification, inflammation, and intimal-medial thickness. Therefore, the objective of our study was to investigate the potential of probiotic supplements to prevent a diet-induced mitochondrial dysfunction in hepatocytes. Apolipoprotein-E knockout mice—genetically modified animals that develop dyslipidemia—were placed in 3 diet groups including a control, western style (high in fats and carbohydrates), as well as a low-carbohydrate high-protein diet. Each group was then further divided in 3 subgroups based on the dose of probiotics administered, including a control, low (0.5 B/dose) and high (5 B/dose) dose of probiotics, for a total of 9 groups (n= 8-12 animals/group). The probiotic supplements contained a 1:1 ratio of Lactobacillus Helveticus and Bifidobacterium Bifidum . The bodyweight and water intake were monitored weekly. After 6 weeks, the liver mitochondria were analyzed by high resolution respirometry using a sequential substrate addition protocol (malate, octanoylcarnitine, ADP, glutamate, pyruvate, cytochrome C, succinate and FCCP) to investigate mitochondrial maximal respiration, leak, membrane damage and uncoupling. Our preliminary results show that the groups that received a high dose of probiotics gained less weight, had a higher respiration following the addition of ADP (a biomarker of complex V efficiency) and a lower respiration following FCCP (a biomarker of mitochondrial uncoupling), as compared to control. Supplements of probiotics could promote weight loss and prevent a diet-induced mitochondrial dysfunction in liver hepatocytes, an important risk factor for NAFLD and therefore, CVD. This project could translate into future research directions in preventative medicine, for example by investigating the potential of probiotics in the prevention of mitochondrial dysfunction in other organs, including the heart and the vascular system.