High Intensity Focused Ultrasound Treatment Attenuates Disease Progression in a Mouse Model of Non‐Alcoholic Steatohepatitis

Non‐alcoholic fatty liver disease (NAFLD), a widespread condition affecting approximately 35% of the US population, is characterized by excessive lipid accumulation in hepatocytes. Non‐alcoholic steatohepatitis (NASH) is a severe form of NAFLD that is characterized by hepatocyte inflammation alongside accumulation of fat in the liver. NASH can lead to cirrhosis and liver cancer. Recent studies suggest that activation of the inflammatory reflex that is mediated by vagus nerve can reduce the chronic inflammation often seen in metabolic disorders including NASH. Here, we utilize a preclinical model of NASH, which is induced by diet, to study the effectiveness of high‐intensity focused ultrasound (HIFU) in modulating specific hepatic neural networks and test HIFU as a therapeutic strategy. Mice in the NASH group were maintained on a high‐fat high‐carbohydrate (HFHC) diet consisting of 60% kcal from fat chow and sugar supplemented water (55% fructose, 45% sucrose), while the low‐fat diet (LFD) control group received 10% kcal from fat chow. After 8 weeks on these diets, animals received daily liver‐targeted HIFU or sham stimulation. Exposure to HIFU but not sham stimulation resulted in significant improvement in body weights (p > 0.05, t test) and blood glucose levels (p > 0.05 t test) in HFHC mice. Moreover, the body weight and blood glucose values of HIFU‐treated HFHC mice trended toward both LFD groups (HIFU‐treated and Sham‐treated). In addition, HIFU attenuated circulating pro‐inflammatory cytokines and metabolic disease markers in HFHC mice. HIFU improved glucose tolerance, reduced HOMA‐IR score, and resulted in less fat accumulation in the liver than Sham‐stimulated HFHC group. Collectively, these findings suggest that noninvasive HIFU stimulation of the liver is a potential therapy for the NASH phenotype. Further studies are necessary to elucidate the mechanism by which liver‐targeted HIFU stimulation reduces inflammation and hepatic fat accumulation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.