Oral Supplementation with Branched-Chain Amino Acids Improves Transthyretin Turnover in Rats with Carbon Tetrachloride-Induced Liver Cirrhosis

Abstract

The hypothesis that dietary branched-chain amino acid (BCAA) supplementation improves the impaired protein turnover in male Donryu rats with carbon tetrachloride-induced liver cirrhosis was tested. We supplemented cirrhotic rats orally for 2 wk with BCAA solution [26.67 mg BCAA/(100 g body weight·d)], a conventional amino acid mixture [4.25 mg BCAA/(100 g body weight·d)] or saline and fed these three groups the AIN76 basal diet to have similar intakes of total energy and total nitrogen. Normal rats without liver cirrhosis were fed the basal diet similar to the above (noncirrhotic controls). After supplementation, rats were fed intravenous transthyretin (thyroxine-binding prealbumin) doubly labeled with 125I-tyramine-cellobiose and 131I. Kinetic indices including production rate of transthyretin were analyzed from plasma transthyretin disappearance curves. Tissue sites of transthyretin degradation were assayed using a trapped ligand technique by measuring 125I-tyramine-cellobiose levels. The production rate of transthyretin was significantly lower in cirrhotic rats supplemented with saline (mean 25.46 × 10-3·h-1) compared with noncirrhotic controls (45.08 × 10-3·h-1) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 × 10-3·h-1, P < 0.05) but not with conventional amino acid mixture (22.49 × 10-3·h-1). The accelerated degradation of transthyretin in muscles of cirrhotic rats was improved by BCAA (P < 0.05). In conclusion, dietary supplementation with BCAA improves the impaired transthyretin turnover in rats with liver cirrhosis.