Background and Aims: In chronic liver disease (CLD) loss of muscle mass (sarcopenia) is highly prevalent which leads to an increased risk in hepatic encephalopathy (HE). Muscle plays a compensatory role during liver disease in clearing ammonia since it contains glutamine synthetase (GS). Therefore, diminished muscle mass leads to a further reduced capacity to remove ammonia. Loss of muscle mass has been described in male rats with CLD but has not been explored in female CLD rats. Our aim was to identify whether sex has an effect on muscle mass and blood ammonia levels. Methods: Five weeks after either BDL (n=8) or Sham (n=8) surgery in male and female rats, the following were assessed; markers of liver injury and function, HE (open field test for anxiety, rota-rod test for motor coordination and night-time activity), body parameters (weight, composition (MRI) and gastrocnemius muscle weight/circumference and grip strength). In addition, muscle GS activity and muscle ammonia clearance as well as glutamine generation (femoral venous-arterial difference) were evaluated in female vs male BDL rats. Results: Female and male BDL rats had similar levels of impaired liver markers (ALP, AST, bilirubin and albumin (p<0.001)) and both developed HE (motor-coordination and night activity (p<0.05)) when compared to respective Shams. Male BDL rats experienced loss of lean mass, muscle weight and strength (p<0.01) while no differences were found in female BDL vs Sham rats. Male and female BDL rats had similar ammonia clearance and glutamine production by muscle, while GS activity was lower in female vs. male BDL rats (p<0.01). Discussion: Our results demonstrate that following BDL surgery, female rats develop CLD and HE comparable to male rats. However, contrary to males, female BDL rats did not develop sarcopenia compared to respective controls. Preserved muscle mass in female BDL did not result in lower blood ammonia (higher ammonia clearance) whereas muscle mass loss in male BDL rats was accompanied with an upregulation in GS which may explain the similar blood ammonia levels found in both male and female BDL rats.
