Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications

Abstract

Pathological increases in cell death in the liver as well as in peripheral tissues has emerged as an important mechanism involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). An increase in hepatocyte cell death by apoptosis is typically present in patients with NAFLD and in experimental models of steatohepatitis, while an increase in adipocyte cell death in visceral adipose tissue may be an important mechanism triggering insulin resistance and hepatic steatosis. The two fundamental pathways of apoptosis, the extrinsic (death receptor-mediated) and intrinsic (organelle-initiated) pathways, are both involved. This article summarizes the current knowledge related to the distinct molecular and biochemical pathways of cell death involved in NAFLD pathogenesis. In particular, it will highlight the efforts for the development of both novel diagnostic and therapeutic strategies based on this knowledge.

Keywords::

• apoptosis
• caspase inhibitor
• cell death
• cytokeratin 18
• fibrosis
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis

Financial & competing interests disclosure

This work was supported by NIH grants DK076852 and DK082451 to Ariel E Feldstein. Ariel E Feldstein is named as co-inventor on pending patents filed by the Cleveland Clinic that refer to the use of biomarkers in fatty liver disorders. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.