Hepatic stellate cell-specific Plvap knockout reveals fasting liver energy metabolism mechanism

A study in mice with hepatic stellate cell-specific Plvap conditional knockout found that HSC PLVAP regulates hepatic insulin signaling and energy substrate preference during fasting. Knockout redistributed fatty acids to skeletal muscle and improved glucose tolerance; the conditional approach avoided confounding phenotypes such as gut leakage seen with global knockout. The effect is context-dependent and reversed by high-fat, high-fructose overnutrition, making PLVAP a potential research target for fatty liver, diabetes and other metabolic diseases.