In-depth analysis of de novo lipogenesis in non-alcoholic fatty liver disease: Mechanism and pharmacological interventions

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by the abnormal buildup of lipids in the liver tissue. Non-alcoholic fatty liver (NAFL) may progress to non-alcoholic steatohepatitis. Triglycerides in the liver can originate from various sources, including de novo lipogenesis (DNL). Research indicates that DNL significantly escalates in NAFLD, worsening steatosis. However, the precise regulatory mechanism of DNL in the development of this disease is not fully understood. Therefore, the targeted reduction of DNL could be a crucial therapeutic strategy. Currently, numerous pharmaceutical agents targeting DNL have been developed, attracting significant attention. This review examines the mechanism of DNL upregulation in NAFLD, assessing its potential as a therapeutic target for hepatic steatosis. Furthermore, we thoroughly examine hepatocellular lipotoxicity and provide an extensive review of the application and limitations of relevant therapeutic drugs, with a focus on key enzymes involved in DNL. The implementation of these pharmacological strategies is expected to significantly improve the management and overall outcomes for patients with NAFLD.

Keywords

• Non-alcoholic fatty liver disease (NAFLD)
• De novo lipogenesis (DNL)
• Therapeutics
• Molecular mechanism