Emerging roles of the acid sphingomyelinase/ceramide pathway in metabolic and cardiovascular diseases: Mechanistic insights and therapeutic implications.

Metabolic diseases have emerged as a leading cause of mortality from non-communicable diseases, posing a significant global public health challenge. Although the association between ceramides (Cers) and metabolic diseases is well-established, the role of the acid sphingomyelinase (ASMase)/Cer pathway in these diseases remains underexplored. This review synthesizes recent research on the biological functions, regulatory mechanisms, and targeted therapies related to the ASMase/Cer pathway in metabolic conditions, including obesity, diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. The effects of the ASMase/Cer pathway on metabolic disease-related indicators, such as glycolipid metabolism, insulin resistance, inflammation, and mitochondrial homeostasis are elucidated. Moreover, this article discusses the therapeutic strategies using ASMase/Cer inhibitors for inverse prevention and treatment of these metabolic diseases in light of the possible efficacy of blockade of the ASMase/Cer pathway in arresting the progression of metabolic diseases. These insights offered herein should provide insight into the contribution of the ASMase/Cer pathway to metabolic diseases and offer tools to develop therapeutic interventions for such pathologies and their severe complications.