Desmosterol

Desmosterol is a cholesterol-like molecule. In the Bloch pathway of cholesterol biosynthesis, Desmosterol is a direct precursor of cholesterol. As an endogenous metabolite, Desmosterol is used to study cholesterol metabolism ^[1]. Desmosterol is an LXR activator and SREBP inhibitor, which can suppress macrophage inflammasome activation and prevent vascular inflammation and atherosclerosis. A reduction in Desmosterol promotes the production of mitochondrial reactive oxygen species (ROS) in macrophages and pyrin domain-dependent inflammasome activation of NLRP3. Desmosterol holds potential for research in inflammation, metabolism, and cardiovascular diseases ^[1][2][3]. In Vitro:Desmosterol depletion (by activating the DHCR24 gene in Dhcr24TG mice to lower Desmosterol levels in macrophages for 4 weeks) inhibits LXR activation, upregulates immune response genes, suppresses cholesterol efflux, thereby leading to lipid accumulation in macrophages and foam cell formation, which is closely associated with the development of atherosclerosis disease ^[2]. In Vivo:Desmosterol depletion (by intraperitoneal injection of Adenovirus (AAV-Cre) to activate the DHCR24 gene in Dhcr24TG mice, thereby reducing Desmosterol levels in macrophages) would suppress LXR activation, upregulate immune response genes, inhibit cholesterol efflux, leading to lipid accumulation in macrophages and foam cell formation, which is closely associated with the development of atherosclerosis disease ^[2].