Background and Aims: In chronic liver disease (CLD), muscle wasting is highly prevalent and leads to an increased risk of hepatic encephalopathy (HE). Since muscle’s glutamine synthetase (GS) compensates for ammonia detoxification during CLD, less muscle leads to a lower capacity to remove ammonia. Muscle loss has been described in male rats but not in female rats with CLD. We aimed to identify whether sex influences muscle mass and blood ammonia levels. Methods: Five weeks after either bile duct ligation (BDL) (n=8) or Sham surgery (n=8) in male and female rats, the following were assessed; markers of liver injury and function, HE (behavioral tests), body weight, and composition (MRI) and, muscle weight, circumference and strength, as well as muscle GS and glutamine generation 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 HE (motor-coordination and activity (p<0.05)) compared to respective Shams. Male BDL, but not female, experienced loss of lean mass, muscle weight, and strength (p<0.01). Male and female BDL had similar muscle ammonia clearance and glutamine production, with lower GS activity in female vs. male BDL (p<0.01). Discussion: Our results demonstrate that although sex did not influence CLD and HE, female rats had preserved muscle mass, which did not result in lower blood ammonia. Contrarily, muscle loss in male rats upregulated GS, which may explain the similar blood ammonia levels found in both male and female BDL rats.
