PMID- 37717561
OWN - NLM
STAT- MEDLINE
DCOM- 20240111
LR  - 20240412
IS  - 1423-0143 (Electronic)
IS  - 1420-4096 (Print)
IS  - 1420-4096 (Linking)
VI  - 48
IP  - 1
DP  - 2023
TI  - Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and 
      Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease.
PG  - 628-641
LID - 10.1159/000533926 [doi]
AB  - INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients 
      with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of 
      the most important clinical features of PEW. Pyroptosis is a type of 
      proinflammatory, programmed cell death associated with skeletal muscle disease. 
      Irisin, as a novel myokine, has attracted extensive attention for its protective 
      role in the complications associated with CKD, but its role in muscle atrophy in 
      CKD is unclear. METHODS: Palmitic acid (PA)-induced muscular atrophy was 
      evaluated by a reduction in C2C12 myotube diameter. Muscle atrophy model was 
      established in male C57BL/6J mice treated with 0.2% adenine for 4 weeks and then 
      fed a 45% high-fat diet. Blood urea nitrogen and creatinine levels, body and 
      muscle weight, and muscle histology were assessed. The expression of carnitine 
      palmitoyltransferase 1A (CPT1A) and pyroptosis-related protein was analysed by 
      Western blots or immunohistochemistry. The release of IL-1beta was detected by 
      enzyme-linked immunosorbent assay. RESULTS: In this study, we showed that 
      PA-induced muscular atrophy manifested as a reduction in C2C12 myotube diameter. 
      During this process, PA can also induce pyroptosis, as shown by the upregulation 
      of NLRP3, cleaved caspase-1 and GSDMD-N expression and the increased IL-1beta 
      release and PI-positive cell rate. Inhibition of caspase-1 or NLRP3 attenuated 
      PA-induced pyroptosis and myotube atrophy in C2C12 cells. Importantly, irisin 
      treatment significantly ameliorated PA-induced skeletal muscle pyroptosis and 
      atrophy. In terms of mechanism, PA upregulated CPT1A, a key enzyme of fatty acid 
      oxidation (FAO), and irisin attenuated this effect, which was consistent with 
      etomoxir (CPT1A inhibitor) treatment. Moreover, irisin improved skeletal muscle 
      atrophy and pyroptosis in adenine-induced mice by regulating FAO. CONCLUSION: Our 
      study firstly verifies that pyroptosis is a novel mechanism of skeletal muscle 
      atrophy in CKD. Irisin ameliorates skeletal muscle atrophy by inhibiting FAO and 
      pyroptosis in CKD, and irisin may be developed as a potential therapeutic agent 
      for the treatment of muscle wasting in CKD patients.
CI  - (c) 2023 The Author(s). Published by S. Karger AG, Basel.
FAU - Zhou, Ting
AU  - Zhou T
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
FAU - Wang, Shiyuan
AU  - Wang S
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
FAU - Pan, Yajing
AU  - Pan Y
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
FAU - Dong, Xingtong
AU  - Dong X
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
FAU - Wu, Leiyun
AU  - Wu L
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
FAU - Meng, Jiali
AU  - Meng J
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
FAU - Zhang, Jialing
AU  - Zhang J
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
FAU - Pang, Qi
AU  - Pang Q
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
AD  - National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, 
      Capital Medical University, Beijing, China.
FAU - Zhang, Aihua
AU  - Zhang A
AD  - Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, 
      China.
AD  - National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, 
      Capital Medical University, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20230915
PL  - Switzerland
TA  - Kidney Blood Press Res
JT  - Kidney & blood pressure research
JID - 9610505
RN  - JAC85A2161 (Adenine)
RN  - EC 3.4.22.- (Caspases)
RN  - 0 (Fibronectins)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 2V16EO95H1 (Palmitic Acid)
SB  - IM
MH  - Animals
MH  - Male
MH  - Mice
MH  - Adenine
MH  - Caspases/metabolism
MH  - Fibronectins
MH  - Mice, Inbred C57BL
MH  - Muscle, Skeletal/pathology
MH  - Muscular Atrophy/drug therapy/metabolism/pathology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - *Palmitic Acid/pharmacology
MH  - Pyroptosis
MH  - *Renal Insufficiency, Chronic/complications/drug therapy/metabolism
PMC - PMC10614467
OTO - NOTNLM
OT  - Chronic kidney disease
OT  - Irisin
OT  - Muscle atrophy
OT  - Pyroptosis
COIS- The authors have no conflicts of interest to declare.
EDAT- 2023/09/18 00:41
MHDA- 2023/12/25 06:42
PMCR- 2023/09/15
CRDT- 2023/09/17 18:23
PHST- 2023/01/26 00:00 [received]
PHST- 2023/08/30 00:00 [accepted]
PHST- 2023/12/25 06:42 [medline]
PHST- 2023/09/18 00:41 [pubmed]
PHST- 2023/09/17 18:23 [entrez]
PHST- 2023/09/15 00:00 [pmc-release]
AID - 000533926 [pii]
AID - 533926 [pii]
AID - 10.1159/000533926 [doi]
PST - ppublish
SO  - Kidney Blood Press Res. 2023;48(1):628-641. doi: 10.1159/000533926. Epub 2023 Sep 
      15.