Hamadan University of Medical Sciences Avicenna Journal of Medical Biochemistry 2345-4113 11 2 2023 12 29 A Decrease in the Activity of Inflammatory and Fibrogenic Pathways in Non-alcoholic Fatty Liver Disease as a Potential Defensive Strategy: A Mini-review 151 154 10.34172/ajmb.2483 EN Sina Mohagheghi https://orcid.org/0000-0003-0388-8095 REVIEW 10.34172/ajmb.2483 2023 12 03 2023 12 20 Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases, from steatosis to cirrhosis. Simple steatosis remains stable over time, and its development into non-alcoholic steatohepatitis (NASH) takes several years. Several pathways are involved in the progression of NAFLD, including the transforming growth factor-β (TGF-β), Hedgehog (Hh), Hippo, and AMP-activated protein kinase (AMPK) signaling pathways. These pathways have a complex interplay, and each pathway can either activate or inhibit other signaling pathways. This review summarizes the evidence implicating that a decline in the activity of the inflammatory and fibrogenic pathways decreases NAFLD. Considering the spectrum of NAFLD and fibrogenic signaling pathways and their cross-talks, it was expected that the activity of the pathways would increase through the occurrence of simple steatosis. However, the expression and activity of fibrogenic signaling pathways decreased in simple steatosis. The levels of Hh ligands, TGF-β1 gene expression, Smad2/3 and P-smad2/3 protein expression, and Taz gene and protein expression decreased in simple steatosis. In addition, the expression of Fos proto-oncogene, AP-1 transcription factor subunit (FOS), MYC, interleukin-1β, early growth response factor 1, and AMPK decreased in simple steatosis. Probably, hepatocyte metabolism is changed in simple steatosis to decrease the risk of production of different oxidative stress molecules, cellular proliferation, and apoptosis, as well as inflammatory and fibrogenic responses, as a potential defensive strategy. However, it should be noted that some changes in the liver tissue metabolism, including AMPK reduction, could be the consequence of high-energy balances in simple steatosis.