Skeletal muscle and NAFLD : preclinical and clinical studies to decode a muscle-to-liver axis
Year: 2021
Type: dissertation
Abstract: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent liver disease in human history. It is estimated that it affects ~25% of the world adult population, hence more than a billion of people globally, making NAFLD one of the most concerning epidemics of the 21st century. In up to 30% of patients with NAFLD, progressive inflammatory changes and hepatocellular ballooning develop over time, a conditioned referred to as Non-Alcoholic Steatohepatitis (NASH). NASH is most frequently asymptomatic and silently leads to end-stage liver disease (i.e. cirrhosis) and hepatocellular carcinoma (HCC) development. Yet, there is still no non-invasive methods to detect patients at-risk for/with NASH. During the past few years, the literature has consistently reported that the status of skeletal muscle compartment has a prognostic value in many chronic diseases. Here, our aims were to define whether (1) NASH was associated by specific structural alterations of the muscle compartment and (2) if those putative changes in muscle structure could participate to NAFLD pathophysiology. Based on several rodent models of NAFLD and on patients cohorts, we found that the presence of NASH was strongly associated with fatty infiltration of the skeletal muscles, i.e. myosteatosis. We demonstrated that evaluating the degree of myosteatosis, assessed with non-invasive imaging methods, had a strong power to distinguish NASH from NAFL, including in early disease stages (i.e. no or mild liver fibrosis). By using an unbiased transcriptomic approach in the muscles of preclinical NAFLD models, we found that myosteatotic muscle of animals with NASH, but not those with NAFL, were characterized by a chronic “viral-like” signature seemingly mediated by type I interferon signaling. By using in-vitro human-derived myotubes, we found that the of exposure muscle cells to fatty acids was able to trigger a type I IFN response. Our study brings build a rationale to explore the plausible implication of a muscle-to-liver axis in NASH pathogenesis.
Author: Nachit, Maxime Younes
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7052041163