Effect of gamma-butyrobetaine on fatty liver in juvenile visceral steatosis mice

We pharmacokinetically examined the effect of gamma -butyrobetaine, a precu rsor of L-carnitine, on th e change of fatty acid meta holism in juvenile v iscera I steatosis (JVS) m ice, wh ich h ave systemic L-ca miti ne deficien cy due to lack of L-carnitine transporter activity. The concentrations of t otal free fatty acid (FFA), palmitic acid and stearic acid in the liver of JVS mice were significantly higher than those in wild-type mice. After intr avenous administration of gamma -butyrobetaine (50 mg kg(-1)), the concentr ation of L-carnitine in the plasma of JVS mice reached about twice that of the control level and levels in the brain, liver and kidney were also signi ficantly increased, whereas those in wild-type mice hardly changed. Althoug h the plasma concentrations of FFA in both types of mi ce were unchanged af ter administration of gamma -butyrobetaine, the concentrations of palmitic acid and stearic acid were significantly decreased. In particular, the live r concentration of FFA in JVS mice was decreased to the wild-type control l evel, accompanied by significant decreases in long-chain fatty acids, palmi tic acid and stearic acid, whereas those in wild-type mice were not changed . These results suggest that gamma -butyrobetaine can be taken up into orga ns, including the liver, of JVS mice, and transformed to L-carnitine. Conse quently, administration of gamma -butyrobetaine may be more useful than tha t of L-carnitine itself for treatment of primary deficiency of carnitine du e to a functional defect of the carnitine transporter.