Genetic Hypercholesterolemic Mice Accumulate Cholesterol in Plasma and Body Due to an Increased Cholesterol Production and Impairment of the Body Cholesterol Clearance

Introduction: It is not known whether cholesterol production is altered in genetic familial hypercholesterolemia.
Objects: Measure plasma and whole body cholesterol, sterol markers of its synthesis and absorption, and sterol fecal excretion in mice models of hypercholesterolemia (LDL Receptor Knockout - LDLRKO and apoE Knockout - APOEKO)
Material and methods: LDLRKO (n=11), APOEKO (n=10) and control (n=10) mice were submitted to a cholesterol-free diet for 12 weeks. In the last 3 days, feces were collected daily. Sterols in plasma, whole body (except head) and feces were measured by GCMS.
Results: Body weight and food intake were similar in all groups. LDLRKO and APOEKO showed a marked increase in cholesterol and synthesis markers in plasma and whole body. APOEKO showed increased sterol fecal excretion and markers of cholesterol absorption (Table).
Conclusions: Both models showed increased cholesterol production (increased desmosterol: Bloch pathway, diminished lathosterol: Kandutsch-Russel pathway) together with a relative impairment of body cholesterol clearance.