Abstract
Background
Based on our previous research conducted on cinnamaldehyde (CA) exhibiting its ability to improve the growth performance of fattening pigs and the adipogenesis induction model of C2C12 cells constructed in our laboratory, we explored the effects of CA on the generation and development of lipid droplets (LDs) in adipogenic differentiated C2C12 cells.
Methods and results
C2C12 cells were treated with either 0.4 mM or 0.8 mM CA. BODIPY staining and triglyceride measurements were conducted to observe the morphology of LDs, and Western blotting was used to measure the expression of their metabolism-related proteins. The results showed that the average number of LDs in the CA treatment groups was more than the control group (P < 0.05), whereas the average LD size and triglyceride content decreased (P < 0.05). Compared with the control group, the expression levels of fusion-related genes in the LDs of the CA treatment group significantly decreased, while decomposition-related genes and autophagy-related genes in the LDs in C2C12 cells significantly increased (P < 0.01).
Conclusion
Cinnamaldehyde promoted the decomposition and autophagy of lipid droplets in C2C12 cells and inhibited the fusion of lipid droplets.
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References
Wood JD, Enser M, Fisher AV et al (2008) Fat deposition, fatty acid composition and meat quality: A review. Meat Sci 78:343–358. https://doi.org/10.1016/j.meatsci.2007.07.019
Cao Z, Hao Y, Fung CW et al (2019) Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain. Nat Commun 10:2902. https://doi.org/10.1038/s41467-019-10835-4
Singh R, Kaushik S, Wang Y et al (2009) Autophagy regulates lipid metabolism. Nature 458:1131–1135. https://doi.org/10.1038/nature07976
Saito T, Kuma A, Sugiura Y et al (2019) Autophagy regulates lipid metabolism through selective turnover of NCoR1. Nat Commun 10:1567. https://doi.org/10.1038/s41467-019-08829-3
Lautaoja JH, Pekkala S, Pasternack A et al (2020) Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling. Biomolecules 10:695. https://doi.org/10.3390/biom10050695
Ranasinghe P, Pigera S, Premakumara GAS et al (2013) Medicinal properties of “true” cinnamon (Cinnamomum zeylanicum): a systematic review. BMC Complement Altern Med 13:275. https://doi.org/10.1186/1472-6882-13-275
Doyle AA, Stephens JC (2019) A review of cinnamaldehyde and its derivatives as antibacterial agents. Fitoterapia 139:104405. https://doi.org/10.1016/j.fitote.2019.104405
Luo Q, Li N, Zheng Z et al (2020) Dietary cinnamaldehyde supplementation improves the growth performance, oxidative stability, immune function, and meat quality in finishing pigs. Livest Sci 240:104221. https://doi.org/10.1016/j.livsci.2020.104221
Khare P, Jagtap S, Jain Y et al (2016) Cinnamaldehyde supplementation prevents fasting-induced hyperphagia, lipid accumulation, and inflammation in high-fat diet-fed mice. BioFactors Oxf Engl 42:201–211. https://doi.org/10.1002/biof.1265
Neto JGO, Boechat SK, Romão JS et al (2020) Treatment with cinnamaldehyde reduces the visceral adiposity and regulates lipid metabolism, autophagy and endoplasmic reticulum stress in the liver of a rat model of early obesity. J Nutr Biochem 77:108321. https://doi.org/10.1016/j.jnutbio.2019.108321
Liu Z, Jun Y, Zhonghao L, Shuqin Mu Starvation-induced lipid droplet morphological remodeling in lipogenic differentiated C2C12 cells[J].China Veterinary Animal Husbandry,2020, 47(11):3460–3466.(in chinese)
Morales PE, Bucarey JL, Espinosa A (2017) Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins. J Diabetes Res 2017:1789395. https://doi.org/10.1155/2017/1789395
Huang B, Yuan HD, Kim DY et al (2011) Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferator-activated receptor-γ (PPARγ) and AMP-activated protein kinase (AMPK) pathways. J Agric Food Chem 59:3666–3673. https://doi.org/10.1021/jf104814t
Khare P, Jagtap S, Jain Y et al (2016) Cinnamaldehyde supplementation prevents fasting-induced hyperphagia, lipid accumulation, and inflammation in high-fat diet-fed mice: Effects of Cinnamaldehyde Supplementation. BioFactors 42:201–211. https://doi.org/10.1002/biof.1265
Cerk IK, Wechselberger L, Oberer M (2018) Adipose Triglyceride Lipase Regulation: An Overview. Curr Protein Pept Sci 19:221–233. https://doi.org/10.2174/1389203718666170918160110
Lee IH, Cao L, Mostoslavsky R et al (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A 105:3374–3379. https://doi.org/10.1073/pnas.0712145105
Sathyanarayan A, Mashek MT, Mashek DG (2017) ATGL Promotes Autophagy/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism. Cell Rep 19:1–9. https://doi.org/10.1016/j.celrep.2017.03.026
Gao G, Chen F-J, Zhou L et al (2017) Control of lipid droplet fusion and growth by CIDE family proteins. Biochim Biophys Acta BBA - Mol Cell Biol Lipids 1862:1197–1204. https://doi.org/10.1016/j.bbalip.2017.06.009
Zhou R, Yi L, Ye X et al (2018) Resveratrol Ameliorates Lipid Droplet Accumulation in Liver Through a SIRT1/ ATF6-Dependent Mechanism. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 51:2397–2420. https://doi.org/10.1159/000495898
Hjelholt AJ, Lee KY, Arlien-Søborg MC et al (2019) Temporal patterns of lipolytic regulators in adipose tissue after acute growth hormone exposure in human subjects: A randomized controlled crossover trial. Mol Metab 29:65–75. https://doi.org/10.1016/j.molmet.2019.08.013
Peng G, Huang E, Ruan J et al (2019) Effects of a high energy and low protein diet on hepatic and plasma characteristics and Cidea and Cidec mRNA expression in liver and adipose tissue of laying hens with fatty liver hemorrhagic syndrome. Anim Sci J Nihon Chikusan Gakkaiho 90:247–254. https://doi.org/10.1111/asj.13140
Yang L, Ding Y, Chen Y et al (2012) The proteomics of lipid droplets: structure, dynamics, and functions of the organelle conserved from bacteria to humans. J Lipid Res 53:1245–1253. https://doi.org/10.1194/jlr.R024117
Chen F, Yin Y, Chua BT, Li P (2020) CIDE family proteins control lipid homeostasis and the development of metabolic diseases. Traffic 21:94–105. https://doi.org/10.1111/tra.12717
Ha HJ, Park HH (2018) Crystal structure and mutation analysis revealed that DREP2 CIDE forms a filament-like structure with features differing from those of DREP4 CIDE. Sci Rep 8:17810. https://doi.org/10.1038/s41598-018-36253-y
Lizaso A, Tan K-T, Lee Y-H (2013) β-adrenergic receptor-stimulated lipolysis requires the RAB7-mediated autolysosomal lipid degradation. Autophagy 9:1228–1243. https://doi.org/10.4161/auto.24893
Sun Z, Gong J, Wu H et al (2013) Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes. Nat Commun 4:1594. https://doi.org/10.1038/ncomms2581
Grahn THM, Zhang Y, Lee M-J et al (2013) FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes. Biochem Biophys Res Commun 432:296–301. https://doi.org/10.1016/j.bbrc.2013.01.113
Xu L, Zhou L, Li P (2012) CIDE proteins and lipid metabolism. Arterioscler Thromb Vasc Biol 32:1094–1098. https://doi.org/10.1161/ATVBAHA.111.241489
Gong J, Sun Z, Wu L et al (2011) Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. J Cell Biol 195:953–963. https://doi.org/10.1083/jcb.201104142
Acknowledgements
This research was supported by the Natural Science Foundation of Tianjin under Grant [18JCQNJC15100], the Tianjin Science and Technology Plan Project under Grant [19ZXZYSN00120, 22ZYCGSN00130], The Pig Industry Technology System Innovation Team in Tianjin under Grant [ITTPRS2021005], the Financial Seed Industry Innovation Research Project of Tianjin Academy of Agricultural Sciences [2022ZYCX009], Gansu Livelihood Science and Technology Project [20210306NCC0180], and the grants from State Key Laboratory of Animal Nutrition of China.
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Y. L., Q. L., Z. L and. X. Z performed the experiment and prepared the draft article; Z. S. and N. L. analyzed data; S. M., Z. Z., and H. Z. provided guidance for the study, J. Y. and C. S. designed the experiment, and acquired funding. All authors contributed to the article and approved the submitted version.
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Liu, Y., Liu, Z., Luo, Q. et al. Cinnamaldehyde affects lipid droplets metabolism after adipogenic differentiation of C2C12 cells. Mol Biol Rep 50, 2033–2039 (2023). https://doi.org/10.1007/s11033-022-08101-w
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DOI: https://doi.org/10.1007/s11033-022-08101-w