Secondary abnormality of carnitine biosynthesis results from carnitine reabsorptional system defect in juvenile visceral steatosis mice

Abstract

We characterized the l-carnitine transport system which is defective in the kidney of juvenile visceral steatosis (JVS) mice by using kidney slices and carnitine-related compounds, and evaluated the influence of the transport defect on the biosynthetic pathway of carnitine. The JVS mouse transport system defect, calculated as the difference in the transport activity between control and JVS mice, was simulated in control by γ-butyrobetaine ( γ-BB) and acetyl l-carnitine. γ-BB hydroxylase activity in the liver of JVS mice was double that of control mice, but the hepatic level of γ-BB in JVS mice was lower than in control mice, suggesting that the conversion of γ-BB to carnitine is not activated in the liver of JVS mice. JVS mice showed higher fractional excretions not only of l-carnitine but also of γ-BB and acetyl l-carnitine than control mice, indicating disturbed reabsorption of γ-BB and acetyl l-carnitine. The disturbed reabsorption of γ-BB in JVS mice is consistent with the fact that the amount of urinary γ-BB in JVS mice was four times that of control. The sum of the concentrations of l-carnitine, acetyl l-carnitine and γ-BB in the urine of JVS mice was not significantly different from that of the control, suggesting no remarkable increase of biosynthesis of γ-BB and carnitine in JVS mice. All these findings suggest that the carnitine transport system plays a role in the transport of γ-BB and that carnitine deficiency is aggravated by the disturbed reabsorption of γ-BB in the kidney.