title: Effect of a low-protein diet supplemented with keto-acids on autophagy and inflammation in 5/6 nephrectomized rats.
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).
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai 200080, China.
authors.forename: Yue-Yue
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai 200080, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai 200080, China.
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai 200080, China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Gu
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai 200080, China.
authors.forename: Jia-Yao
authors.initials: JY
authors.lastname: Ji
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai 200080, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai 200080, China ywj4169@163.com.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001343:Autophagy; D018753:Diet, Protein-Restricted; D019587:Dietary Supplements / Q000032:analysis; D007249:Inflammation / Q000150:complications* / Q000178:diet therapy* / Q000276:immunology / Q000473:pathology; D007651:Keto Acids / Q000627:therapeutic use*; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology; D009133:Muscular Atrophy / Q000178:diet therapy / Q000209:etiology / Q000276:immunology / Q000473:pathology; D009392:Nephrectomy; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000178:diet therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D007651:Keto Acids
keywords: autophagy; chronic kidney disease; inflammation; ketoacids; muscle atrophy