Abstract
Both adipose tissue and skeletal muscle are highly dynamic tissues and interact at the metabolic and hormonal levels in response to internal and external stress, and they coordinate in maintaining whole-body metabolic homeostasis. In our previous study, we revealed that adipocyte-specific Rnf20 knockout mice (ASKO mice) exhibited lower fat mass but higher lean mass, providing a good model for investigating the adipose-muscle crosstalk and exploring the effect of the adipocyte Rnf20 gene on the physiology and metabolism of skeletal muscle. Here, we confirmed that ASKO mice exhibited the significantly increased body weight and gastrocnemius muscle weight. Fiber-type switching in the soleus muscle of ASKO mice was observed, as evidenced by the increased number of fast-twitch fibers and decreased number of slow-twitch fibers. Serum metabolites with significant alteration in abundance were identified by metabolomic analysis and the elevated lysophosphatidylcholine 16:0 [LysoPC (16:0)] was observed in ASKO mice. In addition, lipidome analysis of gonadal white adipose tissue revealed a significant increase in LysoPCs and LysoPC (16:0) in ASKO mice. Furthermore, knockdown of Rnf20 gene in 3T3-L1 cells significantly increased the secretion of LysoPC, suggesting that LysoPC might be a critical metabolite in the adipose-muscle crosstalk of ASKO mice. Furthermore, in vitro study demonstrated that LysoPC (16:0) could induce the expression of fast-twitch muscle fibers related genes in differentiated C2C12 cells, indicating its potential role in adipose-muscle crosstalk. Taken together, these findings not only expand our understanding of the biological functions of Rnf20 gene in systemic lipid metabolism, but also provide insight into adipose tissue dysfunction-induced physiological alterations in skeletal muscle.
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Data availability
The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Abbreviations
- RNF20:
-
Ring finger 20
- WT mice:
-
Wild-type mice
- ASKO mice:
-
Adipocyte-specific Rnf20 knockout mice
- ERK1/2:
-
Extracellular regulated protein kinase 1/2
- GLUT4:
-
Glucose transporter type 4
- IRS-1:
-
Insulin receptor substrate-1
- SREBP1c:
-
Sterol regulatory element binding protein 1c
- NCoR1:
-
Nuclear receptor corepressor 1
- FFA:
-
Free fatty acid
- LPA:
-
Lysophosphatidic acid
- gWAT:
-
Gonadal white adipose tissue
- PBST:
-
Phosphate buffered solution
- BSA:
-
Bovine serum albumin
- CSA:
-
Cross-sectional area
- TAG:
-
Triacylglycerol
- DAG:
-
Diacylglycerol
- CE:
-
Cholesteryl esters
- PC:
-
Phosphatidylcholine
- PE:
-
Phosphatidylethanolamine
- PS:
-
Phosphatidylserine
- LysoPC:
-
Lysophosphatidylcholine
- LysoPE:
-
Lysophosphatidylethanolamine
- LysoPS:
-
Lysophosphatidylserine
- SM:
-
Sphingomyelin
- qRT-PCR:
-
Quantitative reverse transcription PCR
- FBS:
-
Fetal bovine serum
- PCA:
-
Principal component analysis
- FC:
-
Fold change
- PUFA:
-
Polyunsaturated fatty acids
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- SCD-1:
-
Stearoyl-CoA desaturase-1
- PLA2:
-
Phospholipase A2
- Chk:
-
Choline kinase
- Ctα:
-
Phosphocholine cytidylyltransferase α
- Chpt:
-
Choline phosphotransferase
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We thank our lab members for critical reading of the manuscript and helpful discussions.
Funding
This work was supported by Lingnan Modern Agriculture Project (NT2021005), the National Key R & D Program of China (2020YFA0509500 and 2021YFA0805903), National Natural Science Fundation for Distinguished Young Scholars (32025034 and 31925036) and the Agricultural Science and Technology Innovation Program (ASTIP).
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All authors contributed to the study conception and design. The project was designed by YW, JZ and NY. Material preparation, data collection and analysis were performed by YZ, CC, JP, SY, TW and CT. Lipid measurement were performed by GS and SML. The first draft of the manuscript was written by YZ and YW, and all authors commented on previous versions of manuscript. All authors have read and approved the final manuscript.
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This study was performed in line with the principles of Animal Research Panel of the Committee on Research Practice. Approval was granted by Animal Ethics Committee of the Institute of Animal Science (No. IOZ20190077).
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Zhao, Y., Chen, C., Pan, J. et al. Adipocyte Rnf20 ablation increases the fast-twitch fibers of skeletal muscle via lysophosphatidylcholine 16:0. Cell. Mol. Life Sci. 80, 243 (2023). https://doi.org/10.1007/s00018-023-04896-4
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DOI: https://doi.org/10.1007/s00018-023-04896-4