Impaired follistatin secretion in cirrhosis

CONTEXT: Follistatin is a liver-derived inhibitor of the muscle-growth inhibitor myostatin. Reduction in acute follistatin release may help explain muscle loss in liver cirrhosis.

OBJECTIVE: The study aimed to investigate the capacity of acute follistatin release in patients with liver cirrhosis compared to healthy control participants.

DESIGN, SETTING, PARTICIPANTS: To experimentally increase the glucagon-insulin ratio (mimicking the hormonal effect of exercise), we infused glucagon / somatostatin (to inhibit insulin secretion) and compared the acute follistatin increase in eight male cirrhosis patients with eight healthy control participants. Patients and controls received one hour glucagon / somatostatin and saline infusions on two separate days.

MAIN OUTCOME MEASURE: Follistatin was measured during- and five hours following termination of infusions.

RESULTS: The peak follistatin change was significantly decreased in patients with liver cirrhosis compared to healthy control participants (1.9 (Interquartile range: 1.4 to 2.5) versus 3.6 (Interquartile range: 3.0 to 4.0), respectively; p = 0.003). Patients with liver cirrhosis demonstrated significantly decreased amounts of appendicular lean mass compared to healthy controls (27.6 ± 3.8 % versus 34.5 ± 2.9 %, respectively; p = 0.001).

CONCLUSIONS: Patients with cirrhosis show impaired capacity to acutely secrete follistatin. The decrease in acute follistatin release may contribute to loss of muscle mass in liver cirrhosis.