ARB potentiate the Protective Effect of BCAA on Skeletal Muscle Atrophy in Cirrhotic Rats

Objective:
Sarcopenia in patients with cirrhosis implicated in higher rates of mortality. This study investigated the combined effect of angiotensin II receptor blocker (ARB) and branched-chain amino acids (BCAAs) on skeletal muscle atrophy in rats with cirrhosis and steatohepatitis.
Methods:
Male F344 rats are fed a choline-deficient l-amino acid-defined (CDAA) diet for 12 weeks and treated with oral ARB and/or BCAAs. Psoas muscle mass index (PMI) by CT scan and muscle strength were measured, and liver and gastrocnemius specimens were collected.
Results:
CDAA induced remarkable body weight loss, and ARB, but BCAAs did not prevent these changes. PMI was significantly lower in the CDAA group, and ARB and BCAAs inhibited the CDAA-induced reduction of PMI which were enhanced by combined treatment. Treatment with ARB and BCAAs attenuated hepatic inflammation and fibrosis and improved skeletal muscle atrophy and strength in CDAA-fed rats. Both agents reduced intramuscular myostatin and pro-inflammatory cytokine levels, resulting in inhibition of the ubiquitin–proteasome system through interference with the SMAD and NF-κB pathways, respectively. ARB also augmented the BCAA-mediated increase of skeletal muscle mass by promoting insulin growth factor-I production and mitochondrial biogenesis. Moreover, ARB decreased the intramuscular expression of TFEB, a transcriptional inducer of ubiquitin ligase.
Conclusions:
These results indicate that this regimen could serve as a novel treatment for patients with sarcopenia and liver cirrhosis.