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Experts from Axcella Health, AMRA Medical, and VCU discuss the muscle-liver crosstalk and its role in the pathogenesis and treatment of NAFLD/NASH in Frontiers in Endocrinology.
Sweden, Linköping: Tuesday, January 12, 2021 – A perspective review article titled “Harnessing Muscle-Liver Crosstalk to Treat Nonalcoholic Steatohepatitis” was recently published in Frontiers in Endocrinology as part of a special issue of “Non-Alcoholic Steatohepatitis (NASH)—Metabolic Contributors and Therapeutic Targets.” Authored by scientific experts from Axcella Health, AMRA Medical, Linköping University, and Virginia Commonwealth University (VCU), this paper describes the link between muscle composition and chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD). It discusses in depth the scientific basis of underlying factors outside of the liver to treat NAFLD – affecting nearly one-quarter of the world’s adult population.
The report summarizes the current understanding of the association between sarcopenia and NAFLD and outlines the vital role of the muscle–liver axis in the pathogenic cascade of NASH. Furthermore, the authors delineate key mechanisms driving the complex crosstalk between liver and muscle, including metabolic inflexibility and anabolic resistance that collectively impact insulin resistance and systemic inflammation.
To make a case for new NAFLD interventions, the authors leverage extensive clinical evidence linking sarcopenia and muscle composition to NAFLD, such as large meta-analyses linking sarcopenia, high-quality population-based studies, and AMRA’s research involving MRI-based muscle composition profiling of UK Biobank participants. To address NAFLD/NASH’s complex pathogenesis and generate effective treatments, the authors propose exploring interventions that modify muscle mass, muscle fat, and physical function by simultaneously targeting multiple pathways implicated in muscle‒liver crosstalk.
“Muscle wasting appears to be a nearly universal feature in chronic liver disease patients, and while better appreciated in patients with cirrhosis, it is also commonly associated with patients with NASH,” said Dr. Manu Chakravarthy, MD, Ph.D., lead author of the study. He further stated, “Emerging evidence squarely places muscle composition as a key factor impacting outcomes in NAFLD patients, and targeting those dysregulated processes within the liver-muscle axis represents promising therapeutic strategies to address the burden of NAFLD and NASH.”
Learn more by reading the full publication and hearing from three of the authors, Axcella Health’s Dr. Manu Chakravarthy, AMRA Medical’s Dr. Mikael Forsgren, and VCU’s Dr. Mohammad Shadab Siddiqui, in AMRA’s recent webinar.