Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

Bile acids;Sphingolipids;Non-alcoholic fatty liver disease;Non-alcoholic steatohepatitis

Jackson Kaitlyn G.;Way Grayson W.;Zhou Huiping

Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA;Center for Clinical and Translational Research, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA;Central Virginia Veterans Healthcare System, Richmond, VA 23249, USA

中华医学杂志（英文版）

[1]Jackson Kaitlyn G.;Way Grayson W.;Zhou Huiping-.Bile acids and sphingolipids in non-alcoholic fatty liver disease)[J].中华医学杂志（英文版）,2022(10):1163-1171

hepatology,Sphingolipids

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