Abstract
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).
Highlights
The number of chronic kidney disease (CKD) patients has been constantly increasing around the globe
This research team discovered that CKD could result in activation of mitophagy and increased mitochondiral DNA levels in skeletal muscle [13]; consistently, we found this time that activated mitophagy is not capable of clearing abnormal mitochondria which aggravate skeletal muscle wasting through activation of inflammasome mediated by mtDNA and reactive oxygen species (ROS)
Previous studies from this research team found in the Ketosteril Research Award 2010 Foundation Project that, compared with normal-protein diet (NPD) therapy and lowprotein diet (LPD) therapy, LPD+KA therapy could relieve skeletal muscle wasting in rats with diabetic nephropathy and improve the morphological and functional abnormalities of mitochondria [13]
Summary
The number of chronic kidney disease (CKD) patients has been constantly increasing around the globe. Previous studies from this research team found in the Ketosteril Research Award 2010 Foundation Project that, compared with normal-protein diet (NPD) therapy and LPD therapy, LPD+KA therapy could relieve skeletal muscle wasting in rats with diabetic nephropathy and improve the morphological and functional abnormalities of mitochondria [13].
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