Poster Presentation ANZOS-Breakthrough Discoveries Joint Annual Scientific Meeting 2018

Differential benefits of two isocaloric exercise programs on diet-induced non-alcoholic fatty liver disease and circulating extracellular vesicles in mice (#201)

Linda A Ban 1 , Sergio F Martinez Huenchullan 1 2 , Luisa F Olaya Agudo 1 , Babu Raja Maharjan 1 , Christine Yee 1 3 , Charmaine S Tam 4 , Stephen M Twigg 1 5 , Susan V McLennan 1 6
  1. Greg Brown Diabetes and Endocrine Laboratory, University of Sydney, Sydney, NSW, Australia
  2. School of Physical Therapy, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
  3. Ingham Institute, Sydney, NSW, Australia
  4. Northern Clinical School and Centre for Translational Data Science, University of Sydney, Sydney, NSW, Australia
  5. Department of Endocrinology, Univeristy of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia
  6. NSW Health Pathology, Sydney, NSW, Australia

Extracellular vesicles (EVs) are submicron, membrane-bound structures released from activated or stressed cells. They are involved in intercellular signaling and have been shown to be changed in the context of non-alcoholic fatty liver disease (NAFLD), acting as a potential biomarker. While exercise is a commonly prescribed therapeutic intervention for NAFLD, most studies have explored endurance training (END) with few reporting on high-intensity interval training (HIIT). Since little is known about the interaction between exercise and EVs in the context of NAFLD, this study aimed to compare the efficacy of both END and HIIT in their ability to normalise EVs. Ten-week old male C57Bl/6 mice were randomly assigned to high-fat diet (HFD; 45%kcal fat) or standard chow for 20 weeks. After 10 weeks of dietary intervention only, mice were exercised on a treadmill 3x/week for the remaining 10 weeks: 40min at constant 70% maximal running capacity (MRC) for END, or 5min cycles of 85-90% and 50% MRC for HIIT. Physical profile, plasma biochemistry, liver histology and phenotype were compared against untrained groups on either diet. Plasma EVs were isolated by ultracentrifugation and enumerated by NanoSight™. Both exercise protocols reduced liver weight (END: p=0.003; HIIT p<0.001) and improved ALT (both p<0.001) compared to untrained HFD. Liver lipid staining was only decreased by HIIT (END: p=0.532; HIIT: p=0.011), while improvements to the gene expression of tissue remodeling markers (Col1a1, Tgfb1,Timp2) depended upon the protocol. Although HFD had a negligible effect on EVs, they were increased by 2-fold after END training, independent of diet (HFD: p=0.068; chow: p=0.014). While exercise is effective in reducing NAFLD burden, changes to steatosis or tissue remodeling are affected by the specific protocol. Interestingly, exercise had a stronger effect on EV number than obesity. While the literature implicates vascular events, the mechanisms in our model are currently under investigation.