Dysregulated Lipid Metabolism in Hepatocellular Carcinoma: Mechanisms and Therapeutic Strategies

ABSTRACT

Hepatocellular carcinoma (HCC) is a prevalent and aggressive malignancy with rising incidence and mortality rates worldwide. Accumulating evidence indicates that dysregulated lipid metabolism is crucial in HCC development, progression, and treatment resistance, making it a promising target for prevention and intervention against HCC. However, a comprehensive understanding of the heterogeneity of lipid metabolism in HCC driven by distinct etiologies, its role in HCC progression and immunosuppression, and the relevant molecular mechanisms remains limited, which impedes advances in strategies targeting lipid metabolism. This review introduces the primary pathways of hepatic lipid metabolism, encompassing intake, synthesis, storage, catabolism, and excretion of lipids. It also summarizes the mechanisms underlying aberrant lipid metabolism in HCC and the molecular drivers of lipid dysregulation during hepatocarcinogenesis. Furthermore, this review delineates the hallmarks of lipid metabolic reprogramming in HCC cells, and highlights the impact of disordered lipid metabolism on malignant potential of HCC cells and the immunosuppressive tumor microenvironment. Finally, the strategies for harnessing lipid metabolism to prevent and treat HCC are emphatically discussed. By integrating these insights, this review deepens the understanding of the relationship between lipid metabolism and HCC, laying a foundation for optimizing preventive and therapeutic strategies against this malignancy.