Fig. 1

Schematic overview of normal cholesterol physiology and possible mechanisms involved cholesterol disturbances during critical illness. In normal physiology, dietary cholesterol is taken up from the intestine and stored as cytosolic lipid droplets or packed into lipoproteins to enable transport in the circulation. Cholesterol can be converted and excreted as bile acids as part of the enterohepatic circulation or converted to steroid hormones. The liver is the main organ for de novo synthesis of cholesterol from Acetyl CoA through the mevalonate pathway, for which HMGCR is the key-regulator. During critical illness, reduced dietary uptake and reduced bile acid excretion are involved in a disturbed enterohepatic circulation. Cholesterol synthesis appears reduced. Increased shuttling to tissue repair, LPS scavenging and conversion to steroid hormones might all play a role. LPS: lipopolysaccharide; TLR 4: toll-like receptor 4; CD14: cluster of differentiation 14; HMGCR: HMG-CoA reductase. SR-BI: scavenger receptor class B type I; LDL-R: LDL-receptor. Created with BioRender.com