TGF-β1 signaling can worsen NAFLD with liver fibrosis backdrop

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of fats in the liver. Relatively benign NAFLD often progresses to fibrosis, cirrhosis, and liver malignancies. Although NAFLD precedes fibrosis, continuous lipid overload keeps fueling fibrosis and the process of disease progression remains unhindered. It is well known that TGF-β1 plays its part in liver fibrosis, yet its effects on liver lipid overload remain unknown. As TGF-β1 signaling has been increasingly attempted to manage liver fibrosis, its actions on the primary suspect (NAFLD) are easily ignored. The complex interaction of inflammatory stress and lipid accumulation aided by mediators scuh as pro-inflammatory interleukins and TGF-β1 forms the basis of NAFLD progression. Anticipatorily, the inhibition of TGF-β1 signaling during anti-fibrotic treatment should reverse the NAFLD though the data remain scattered on this subject to date. TGF-β1 signaling pathway is an important drug target in liver fibrosis and abundant literature is available on it, but its direct effects on NAFLD are rarely studied. This review aims to cover the pathogenesis of NAFLD focusing on the role of the TGF-β1 in the disease progression, especially in the backdrop of liver fibrosis.

Keywords: Non-alcoholic fatty liver disease; Oxidative stress; Pathogenesis; Reactive oxygen species; Treatment.