Abstract
Muscle tissue influences energy and protein metabolism throughout the body. Earlier reports demonstrated that bone morphogenetic protein 11 (BMP11) could inhibit skeleton muscle proliferation and development. However, the role of BMP11 in the fatty acid metabolism of muscle has not been explored. In this study, we investigated the physiological functions of exogenous BMP11 on lipid metabolism in C2C12 cells using recombinant BMP11 (rBMP11). Treatment by rBMP11 inhibits myogenesis while inducing lipid accumulation in C2C12 cells. Moreover, induction of rBMP11 inhibits not only fatty acid uptake by downregulation of the fatty acid transport proteins CD36, FATP1, FATP4, and FABP3 but also suppresses fatty acid oxidation by decreasing the levels of p-HSL, ATGL, ACSL, and CGI-58 via Smad 2/3 pathway. Taken together, BMP11 negatively regulates lipid metabolism in muscle cells, which is an opposite result to that in adipocytes where BMP11 improves metabolic homeostasis. Considering the contrasting roles of BMP11 in adipocytes and muscle cells, BMP11 could be a promising target for pharmacological intervention in the treatment of metabolic diseases.
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Abbreviations
- Abhd5 :
-
gene encoding CGI-58
- Acvrl1 :
-
gene encoding activin receptor-like kinase 1 (ALK1)
- Acvr1 :
-
gene encoding activin receptor-like kinase-2 (ALK2)
- Acvr1b :
-
gene encoding activin receptor type-1B (ALK4)
- Acvr2a :
-
gene encoding activin receptor type-2A (ACTRIIA)
- Acvr2b :
-
gene encoding activin receptor type-2B (ACTRIIB)
- ACOX1 :
-
acyl-coenzyme A oxidase 1
- ACSL :
-
long-chainfatty-acid-CoA ligase
- ATGL :
-
adipose triglyceride lipase
- BMP :
-
bone morphogenetic protein
- Bmpr1a :
-
gene encoding bone morphogenetic protein receptor type-1A (ALK3)
- Bmpr1b :
-
gene encoding bone morphogenetic protein receptor type-1B (ALK6)
- Bmpr2 :
-
gene encoding bone morphogenetic protein receptor type 2 (BMPRII)
- CD36 :
-
cluster of differentiation 36
- CGI-58 :
-
comparative gene identification-58
- CPT1 :
-
carnitine palmitoyltransferase 1
- FFA :
-
free fatty acid
- FAS :
-
fatty acid synthase
- FATP4 :
-
long-chain fatty acid transport protein 4
- GDF11 :
-
growth differentiation factor-11
- MYH/Myh :
-
myosin heavy chain/encoding gene
- MYOG/Myog :
-
myogenin/encoding gene
- p-HSL :
-
phosphorylated hormone-sensitive lipase
- Plin :
-
gene encoding perilipin
- Slc27a :
-
gene encoding FATP
- Tbx1 :
-
gene encoding T-box protein 1
- Tgfbr-1 :
-
transforming growth factor beta receptor type 1 (ALK5)
- TG :
-
triglyceride
- UCP/Ucp :
-
uncoupling protein/encoding gene.
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Acknowledgments
This work was supported by a National Research Foundation of Korea grant funded by the Korean government (MSIT) (No. 2019R1A2C2002163).
The authors declare no conflict of interest.
Neither ethical approval nor informed consent was required for this study.
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Pham, H.G., Park, J.P. & Yun, J.W. BMP11 Negatively Regulates Lipid Metabolism in C2C12 Muscle Cells. Biotechnol Bioproc E 25, 670–680 (2020). https://doi.org/10.1007/s12257-020-0254-8
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DOI: https://doi.org/10.1007/s12257-020-0254-8