MicroRNA-124 promotes hepatic triglyceride accumulation through targeting tribbles homolog 3
Open accessAbstract
An increase in hepatic triglyceride (TG) contents usually results in non-alcoholic fatty liver disease (NAFLD) and related metabolic diseases. However, the mechanisms underlying perturbations of hepatic TG homeostasis remain largely unknown. Here, we showed that MicroRNA-124 was up-regulated in the livers of C57BL/6 mice fed a short-term high-fat-diet (HFD). Adenoviral overexpression of miR-124 in C57BL/6 mice led to accumulation of excessive triglycerides and up-regulation of lipogenic genes in the liver. We further identified tribbles homolog 3 (TRB3) as a direct target of miR-124. AKT signaling, which is negatively regulated by TRB3, was enhanced by miR-124 overexpression. Moreover, restoration of TRB3 expression markedly abolished the effect of miR-124 on hepatic TG metabolism. Therefore, our findings revealed that miR-124 played a role in mediating high-fat-diet induced TG accumulation in the liver.
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Such mechanisms may not be microglia-specific because miR-124 has been shown to increase fatty acid and triglyceride content in liver cells.
“However, such mechanisms may not be microglia-specific due to the fact that miR-124 has been shown to increase fatty acid and triglyceride content in liver cells [66, 67].”
From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [67]
The Results section, “miR-124 promotes hepatic TG accumulation” (page unavailable), reports that miR-124 overexpression increased triglyceride content in mouse livers. It does not report an increase in fatty acid content, so that part of the attributed claim is unsupported. (LLM, conf=0.86)
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Cites
The HCV Life Cycle: In vitro Tissue Culture Systems and Therapeutic Targets
Gerold, G., & Pietschmann, T. (2014) · Digestive Diseases · doi:10.1159/000360830 · Cited by 4,854 · see citing works
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769 · see citing works
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,285 · see citing works
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092 · see citing works
Human Fatty Liver Disease: Old Questions and New Insights
Cohen, J. C., Horton, J. D., & Hobbs, H. H. (2011) · Science · doi:10.1126/science.1204265 · Cited by 2,089 · see citing works
MicroRNAs in metabolism and metabolic disorders
Rottiers, V., & Näär, A. M. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3313 · Cited by 1,156 · see citing works
Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease
Kawano, Y., & Cohen, D. E. (2013) · Journal of Gastroenterology · doi:10.1007/s00535-013-0758-5 · Cited by 968 · see citing works
Lipid Metabolism and Liver Inflammation. II. Fatty liver disease and fatty acid oxidation
Reddy, J. K., & Rao, M. S. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00521.2005 · Cited by 860 · see citing works
TRB3: A <i>tribbles</i> Homolog That Inhibits Akt/PKB Activation by Insulin in Liver
Du, K., Herzig, S., Kulkarni, R. N., & Montminy, M. (2003) · Science · doi:10.1126/science.1079817 · Cited by 842 · see citing works
MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis
Tsai, W.-C., Hsu, S., Hsu, C.-S., Lai, T., Chen, S.-J., Shen, R., Huang, Y., Chen, H., Lee, C.-H., Tsai, T., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63455 · Cited by 815 · see citing works
Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver
Hsu, S., Wang, B., Kota, J., Yu, J., Costinean, S., Kutay, H., Yu, L., Bai, S., Perle, K. L., Chivukula, R. R., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63539 · Cited by 776 · see citing works
Kammoun, H. L., Chabanon, H., Hainault, I., Luquet, S., Magnan, C., Koike, T., Ferré, P., & Foufelle, F. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37007 · Cited by 732 · see citing works
Shimomura, I., Bashmakov, Y. K., & Horton, J. D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30028 · Cited by 704 · see citing works
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos, A., Goedeke, L., Smibert, P., Ramírez, C. M., Warrier, N. P., Andreo, U., Cirera-Salinas, D., Rayner, K., Suresh, U., Pastor-Pareja, J. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102281108 · Cited by 670 · see citing works
PGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3
Koo, S.-H., Satoh, H., Herzig, S., Lee, C.-H., Hedrick, S., Kulkarni, R., Evans, R. M., Olefsky, J., & Montminy, M. (2004) · Nature Medicine · doi:10.1038/nm1044 · Cited by 550 · see citing works
Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation*
Gerin, I., Clerbaux, L.-A., Haumont, O., Lanthier, N., Das, A. K., Burant, C. F., Leclercq, I. A., MacDougald, O. A., & Bommer, G. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152090 · Cited by 382 · see citing works
Zheng, F., Liao, Y.-J., Cai, M.-Y., Liu, Y.-H., Liu, T.-H., Chen, S.-P., Bian, X., Guan, X., Lin, M. C.-M., Zeng, Y.-X., et al. (2011) · Gut · doi:10.1136/gut.2011.239145 · Cited by 376 · see citing works
The Akt-SREBP nexus: cell signaling meets lipid metabolism.
Krycer, J., Sharpe, L. J., Luu, W., & Brown, A. J. (2010) · Trends in endocrinology and metabolism · doi:10.1016/j.tem.2010.01.001 · Cited by 347 · see citing works
MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic β-Cell Lines*
Baroukh, N., Ravier, M. A., Loder, M. K., Hill, E. V., Bounacer, A., Scharfmann, R., Rutter, G. A., & Van Obberghen, E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611841200 · Cited by 326 · see citing works
Agirre, X., Vilas‐Zornoza, A., Jiménez‐Velasco, A., Martín-Subero, J. I., Cordeu, L., Gárate, L., José‐Eneriz, E. S., Abizanda, G., Rodríguez‐Otero, P., Fortes, P., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4025 · Cited by 302 · see citing works
Ando, T., Yoshida, T., Enomoto, S., Asada, K., Tatematsu, M., Ichinose, M., Sugiyama, T., & Ushijima, T. (2008) · International Journal of Cancer · doi:10.1002/ijc.24219 · Cited by 279 · see citing works
Lovis, P., Gattesco, S., & Regazzi, R. (2008) · bchm · doi:10.1515/bc.2008.026 · Cited by 257 · see citing works
Methylation-mediated silencing and tumour suppressive function of hsa-miR-124 in cervical cancer
Wilting, S. M., van Boerdonk, R. A. A., Henken, F. E., Meijer, C. J. L. M., Diosdado, B., Meijer, G. A., le Sage, C., Agami, R., Snijders, P. J. F., & Steenbergen, R. D. M. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-167 · Cited by 255 · see citing works
miR-124 Inhibits STAT3 Signaling to Enhance T Cell–Mediated Immune Clearance of Glioma
Wei, J., Wang, F., Kong, L.-Y., Xu, S., Doucette, T. A., Ferguson, S. D., Yang, Y., McEnery, K., Jethwa, K. R., Gjyshi, O., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4318 · Cited by 253 · see citing works
Decreased lipid synthesis in livers of mice with disrupted Site-1 protease gene
Yang, J., Goldstein, J. L., Hammer, R. E., Moon, Y.-A., Brown, M. S., & Horton, J. D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201524598 · Cited by 237 · see citing works
Carter-Kent, C. A., Zein, N. N., & Feldstein, A. E. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01709.x · Cited by 202 · see citing works
MicroRNAs: regulators of neuronal fate
Sun, A. X., Crabtree, G. R., & Yoo, A. S. J. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.12.007 · Cited by 176 · see citing works
Shi, X.-B., Xue, L., Ma, A.-H., Tepper, C. G., Gandour‐Edwards, R. F., Kung, H.-J., & White, R. D. (2012) · Oncogene · doi:10.1038/onc.2012.425 · Cited by 168 · see citing works
Ono, H., Shimano, H., Katagiri, H., Yahagi, N., Sakoda, H., Onishi, Y., Anai, M., Ogihara, T., Fujishiro, M., Viana, A. Y. I., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2905 · Cited by 168 · see citing works
Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective
Wong, R. H.-F., & Sul, H. S. (2010) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2010.08.004 · Cited by 160 · see citing works
A Phosphorylation Cascade Controls the Degradation of Active SREBP1*
Bengoechea-Alonso, M., & Ericsson, J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807906200 · Cited by 144 · see citing works
Xiong, X., Wang, X., Lu, Y., Wang, E., Zhang, Z., Yang, J., Zhang, H., & Li, X. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.12.003 · Cited by 140 · see citing works
Self-citationYellaturu, C. R., Deng, X., Cagen, L. M., Wilcox, H. G., Mansbach, C. M., Siddiqi, S. A., Park, E. A., Raghow, R., & Elam, M. B. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m805746200 · Cited by 138 · see citing works
Punga, T., Bengoechea-Alonso, M., & Ericsson, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604983200 · Cited by 136 · see citing works
Liu, W., Cao, H., Cheng, Y., Chang, C., Lü, M., Jing, Y., Zhang, D., Yao, X., Duan, Z., Xia, H., et al. (2014) · Nature Communications · doi:10.1038/ncomms6684 · Cited by 114 · see citing works
Converging miRNA functions in diverse brain disorders: A case for miR-124 and miR-126
Sonntag, K., Woo, T.-U. W., & Krichevsky, A. M. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.11.035 · Cited by 104 · see citing works
Yin Yang 1 promotes hepatic steatosis through repression of farnesoid X receptor in obese mice
Lu, Y., Ma, Z., Zhang, Z., Xiong, X., Wang, X., Zhang, H., Shi, G., Xia, X., Ning, G., & Li, X. (2013) · Gut · doi:10.1136/gutjnl-2012-303150 · Cited by 100 · see citing works
Self-citationOkamoto, H., Latres, E., Liu, R., Thabet, K., Murphy, A. J., Valenzeula, D., Yancopoulos, G. D., Stitt, T. N., Glass, D. J., & Sleeman, M. W. (2007) · Diabetes · doi:10.2337/db06-1448 · Cited by 79 · see citing works
Dual Role of MicroRNAs in NAFLD
Ceccarelli, S., Panera, N., Gnani, D., & Nobili, V. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14048437 · Cited by 66 · see citing works
STAT3 is involved in miR-124-mediated suppressive effects on esophageal cancer cells
Cheng, Y., Li, Y., Nian, Y., Liu, D., Dai, F., & Zhang, J. (2015) · BMC Cancer · doi:10.1186/s12885-015-1303-0 · Cited by 62 · see citing works
Self-citationYu, J., Xiao, F., Guo, Y., Deng, J., Liu, B., Zhang, Q., Li, K., Wang, C., Chen, S., & Guo, F. (2014) · Diabetes · doi:10.2337/db14-1368 · Cited by 45 · see citing works
Self-citationElam, M. B., Yellaturu, C. R., Howell, G., Deng, X., Cowan, G. S. M., Kumar, P., Park, E. A., Hiler, M. L., Wilcox, H. G., Hughes, T. A., et al. (2009) · Metabolism · doi:10.1016/j.metabol.2009.09.001 · Cited by 29 · see citing works
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Yu, Q., Chopp, M., & Chen, J. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113382 · Cited by 58 · see citing works
Song, X., Zhang, L., Li, Q., Li, Y., Ding, F., & Li, X. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118821 · Cited by 48 · see citing works
Self-citationLai, C., Lin, C.-Y., Hsu, C.-C., Yeh, K.-Y., & Her, G. M. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.04.009 · Cited by 42 · see citing works
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Chhichholiya, Y., Suryan, A. K., Suman, P., Munshi, A., & Singh, S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.793523 · Cited by 41 · see citing works
Shu, K., & Zhang, Y. (2019) · Cell Stress and Chaperones · doi:10.1007/s12192-019-01031-w · Cited by 37 · see citing works
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Mirra, P., Nigro, C., Prevenzano, I., Leone, A., Raciti, G. A., Formisano, P., Bèguinot, F., & Miele, C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00046 · Cited by 36 · see citing works
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Shaw, T. A., Singaravelu, R., Powdrill, M. H., Nhan, J., Ahmed, N., Özcelik, D., & Pezacki, J. P. (2018) · iScience · doi:10.1016/j.isci.2018.11.028 · Cited by 34 · see citing works
Chen, R., Liao, X., Chen, F., Wang, B., Huang, J., Jian, G., Huang, Z., Yin, G., Liu, H., & Jin, D. (2018) · PubMed Central · Cited by 26 · see citing works
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Dobens, L., Nauman, C., Fischer, Z., & Yao, X. (2021) · Cancers · doi:10.3390/cancers13040883 · Cited by 23 · see citing works
Fang, Q., Shen, Q., Li, J., Yang, Y., Guo, J., Cheng, Y., Zhou, H., Niu, W., Chen, L., Li, C., et al. (2019) · Hepatology Research · doi:10.1111/hepr.13330 · Cited by 19 · see citing works
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Zan, T., Li, P., Yang, X., Gu, Y., & Liu, B. (2019) · Experimental Physiology · doi:10.1113/ep087963 · Cited by 6 · see citing works
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- Authors
- Liu, X., Zhao, J., Liu, Q., Xiong, X., Zhang, Z., Jiao, Y., Li, X., Liu, B., Li, Y., & Lu, Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Xiamen University (CN)
- Fudan University (CN)
- Hubei Polytechnic University (CN)
- Corresponding author
- Li, Yao
- Venue
- Scientific Reports
- Published
- 2016-11-15
- Volume
- 6
- Issue
- 1
- Pages
- 37170-37170
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5109039
- OpenAlex
- W2556020677
- Cited by
- 25
- References
- 42
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 6
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81500617, 81300700, 81570769, 31530033)
- Shanghai Jiao Tong University
- School of Medicine, Shanghai Jiao Tong University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- miR-124, TRB3, hepatic triglyceride accumulation, non-alcoholic fatty liver disease, high-fat diet, Akt signaling, lipogenesis, microRNA target regulation, hepatic lipid metabolism
- MeSH terms
- Adenoviridae, Animals, Dietary Fats, Liver, Male, Triglycerides, Cell Cycle Proteins, MicroRNAs, Lipogenesis, Proto-Oncogene Proteins c-akt, Mice
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