Non-alcoholic fatty liver disease (NAFLD) is a global health concern and a clinicopathological syndrome characterized by excessive fat deposition in hepatocytes. It develops in the absence of alcohol intake or other established liver-damaging factors, encompassing a spectrum from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), which may or may not progress to cirrhosis. Abnormal lipid metabolism plays a central role in NAFLD progression, driven by genetic mutations, dysregulation of transcription factors, and altered lipid species. This review introduces key genetic factors, such as TM6SF2, PNPLA3, and MBOAT7, which contribute to lipid accumulation and liver inflammation, and discusses transcription factors like SREBP1c and PPARγ that promote lipogenesis, exacerbating hepatic fat buildup. This review also explores Lipid species like triglycerides, free fatty acids, and ceramides act as signaling molecules, influencing metabolic pathways and contributing to insulin resistance, inflammation, and fibrosis. Additionally, this review discusses signaling pathways such as mTOR and AMPK modulate lipid metabolism and impact NAFLD progression. Understanding these molecular mechanisms offers potential therapeutic targets to mitigate the metabolic disturbances in NAFLD and develop effective treatments for this increasingly prevalent disease.
