Background: Malnutrition is an important prognostic factor potentially influencing clinical outcome of patients suffering from chronic liver disease (CLD). Malnutrition, considered a consequence of metabolic disturbances (hypermetabolism), exacerbates sarcopenia (severe muscle loss) and hepatic encephalopathy (complex neuropsychiatric disorder) in cirrhotic patients. New management strategies focussing on improving nutritional status and attenuating CLD-related complications are an unmet clinical need. We hypothesize supplementation with branched-chain amino acid isoleucine (ILE) and exercise could possibly attenuate muscle mass loss and prevent brain edema, a common entity of hepatic encephalopathy, in CLD. Methods: CLD was induced in rats following 6-week bile-duct ligation (BDL). Five experimental groups were tested; 1) BDL; 2) BDL + ILE; 3) BDL + EX; 4) BDL + ILE + EX; 5) Sham-operated rats. Two weeks following BDL, rats were submitted to 15 min exercise (10 cm/s) every other day and BDL rats receiving ILE, were gavaged daily (1.5 mg/kg) for 4 weeks. Body weight, muscle (gastrocnemius) mass, metabolic state (calculation of energy expenditure independent of food intake and fecal mass) and cerebral edema (specific gravity method) were measured in all groups. Results: BDL rats gained less body weight (33.7 6.3 g vs 204.5 26.0 g; p < 0.01) and muscle mass (weight/body weight ratio) (0.0047 0.0002 vs 0.0051 0.0002; p < 0.05) compared to sham-operated rats, respectively. ILE-treated BDL rats submitted to exercise demonstrated an increase in weight gain and an increase in muscle mass (weight/body weight ratio) (0.0056 0.0003 vs 0.0047 0.0003; p < 0.05) and an attenuation in hypermetabolic status, compared to BDL rats respectively. ILE+exercsie also attenuated brain water content in BDL rats. Conclusion: Our results demonstrate that supplemental ILE along with exercise reduces body weight and muscle mass loss, improves metabolic activity and attenuates brain edema. These findings suggest that strategies aiming at improving nutritional status and preventing muscle mass loss will attenuate the onset of sarcopenia and hepatic encephalopathy, and therefore improve outcome in CLD. EX and ILE supplementation could rapidly be translated into clinical practice.
