New insight into sortilin in controlling lipid metabolism and the risk of atherogenesis

Dyslipidemia, including increased plasma levels of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol and triglyceride, and decreased plasma levels of high-density lipoprotein cholesterol, has been considered a key factor associated with a series of health problems grouped together as metabolic syndrome. Worldwide, dyslipidemia has become a pressing issue, together with the rising prevalence of metabolic syndrome and cardiovascular disease (CVD). Recently, multiple genome-wide association studies and experimental analyses have been used to assess the underlying genetic basis of lipid metabolism and to identify novel gene loci that contribute to the alterations in lipid levels. The results have demonstrated that sortilin, which is encoded by SORT1, plays an important role in modulating the level of LDL-C and the risk of CVD. Herein, we summarize the current understanding of the role of sortilin in the pathogenesis of dyslipidemia and atherosclerosis. Furthermore, we provide new insights into the potential mechanisms by which sortilin affects lipid metabolism in hepatocytes, adipocytes, and macrophages.