Ketoacids (KA) are known to preserve muscle mass among patients with
chronic kidney disease (CKD) on a
low-protein diet (LPD). The present study was to compare the effects of KA supplemented
diet therapy in autophagy and
inflammation in CKD rats' skeletal muscle. Rats with 5/6
nephrectomy were randomly divided into three groups and fed with either 11 g/kg/day
protein [normal-
protein diet (
NPD)], 3 g/kg/day
protein (LPD) or 3 g/kg/day
protein which including 5%
protein plus 1% KA (LPD + KA) for 24 weeks.
Sham-operated rats with
NPD intake were used as control. LPD could improve
body weight, gastrocnemius muscle mass, as well as gastrocnemius muscle cross-sectional area, with the effect being more obvious in the LPD + KA group. The autophagy marker LC3 (
microtubule-associated protein 1 light chain 3), p62, Parkin and
PTEN induced putative kinase 1 (PINK1) were significantly attenuate in LPD + KA group than LPD group. LPD + KA group had the lower total
mtDNA (mitochondiral
DNA) and cytosol
mtDNA, NACHT-PYD-containing
protein 3 (NALP3)
inflammasome than LPD group, but its
reactive oxygen species (ROS), caspase-1 and apoptosis-associated speck-like
protein containing a CARD (ASC) level was higher. Immunoblotting showed IL-1β (interleukin-1-beta) was lower in LPD and LPD + KA group than the
NPD group, but
IL-18 showed no significant difference among control and CKD group;
toll-like receptor signalling-dependent
IL-6 was higher in LPD + KA group than LPD group, but
tumor necrosis factor-α (TNF-α) was not significantly changed between LPD + KA and LPD group. Systematic changes of the four
cytokines were different from that of the tissue. Although LPD + KA could further ameliorate-activated autophagy than LPD, its effect on the activated
inflammation state in CKD was not distinctly. Further study is still required to explore the method of ameliorating
inflammation to provide new therapeutic approaches for CKD
protein energy wasting (PEW).