In the studies reported here, we investigated the role of skeletal muscle mass in the regulation of liver:body mass ratio and liver regeneration via the analysis of myostatin-null mice, in which skeletal muscle is hypertrophied.
The results showed that liver mass is comparable and liver:body mass significantly diminished in the null animals compared to age-, sex-, and strain-matched controls.
In association with these findings, basal hepatic Akt signaling is decreased, and the expression of the target genes of the constitutive androstane receptor and the integrin-linked kinase are dysregulated in the myostatin-null mice.
In addition, the baseline expression levels of the regulators of the G1-S phase cell cycle progression in liver are suppressed in the null mice.
The initiation of liver regeneration is not impaired in the null animals, although it progresses toward the lower liver:body mass set point.
The data show that skeletal muscle is not the body component against which liver mass is positively regulated, and thus they demonstrate a previously unrecognized systemic compartmental specificity for the regulation of liver:body mass ratio.