Maternal betaine protects rat offspring from glucocorticoid-induced activation of lipolytic genes in adipose tissue through modification of DNA methylation
Abstract
Purpose Excessive exposure of glucocorticoids activates adipose lipolysis, increases circulating free fatty acids, and contributes to ectopic lipid deposition in liver and skeletal muscle. Our previous study demonstrated that maternal betaine supplementation attenuates glucocorticoid-induced hepatic lipid accumulation in rat offspring. However, it is unclear whether maternal betaine supplementation is effective in preventing glucocorticoid-induced lipolysis in the adipose tissue of offspring.Methods In this study, 20 pregnant rats were fed with basal or betaine-supplemented (10 g/kg) diets throughout gestation and lactation, and the offspring rats were raised on the basal diet from weaning till 3 months of age followed by daily intraperitoneal injection of saline or 0.1 mg/kg dexamethasone (DEX) for 3 weeks.Results Chronic DEX treatment significantly (P < 0.05) decreased serum corticosterone level and increased proinflammatory cytokines, such as TNFα, IL-1β, and IL-6. Meanwhile, GR protein content in adipose tissue was increased in response to DEX treatment, which was associated with a significant (P < 0.05) up-regulation of ATGL and HSL expression at both mRNA and protein levels. All these DEX-induced changes were significantly (P < 0.05) attenuated in progeny rats derived from betaine-supplemented dams. Furthermore, DEX-induced hypomethylation of ATGL and HSL gene promoters was reversed by maternal betaine supplementation.Conclusions Taken together, these results suggest that maternal betaine supplementation is effective in alleviating glucocorticoid-induced lipolysis in adipose tissue with modification of DNA methylation on the promoter of lipolytic genes.
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Methylation of the HSL promoter can downregulate HSL expression, reducing lipolytic activity and fat mobilization capacity.
“For instance, methylation of the HSL promoter can downregulate HSL expression, reducing lipolytic activity and fat mobilization capacity [73].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [73]
Epigenetic modifications in genes governing lipolysis, such as HSL and ATGL, affect the ability to mobilize fat stores.
“Epigenetic modifications in genes governing lipolysis, such as HSL and adipose triglyceride lipase (ATGL), affect the ability to mobilize fat stores.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [73]
Cites
Burdge, G. C., Slater-Jefferies, J. L., Torrens, C., Phillips, E. S., Hanson, M. A., & Lillycrop, K. A. (2007) · British Journal Of Nutrition · doi:10.1017/s0007114507352392 · Cited by 418 · see citing works
Mechanisms of Glucocorticoid-Induced Insulin Resistance
Geer, E. B., Islam, J., & Buettner, C. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.10.005 · Cited by 392 · see citing works
The role of the glucocorticoid receptor in inflammation and immunity
Baschant, U., & Tuckermann, J. P. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.03.058 · Cited by 354 · see citing works
Keating, S. T., & El‐Osta, A. (2015) · Circulation Research · doi:10.1161/circresaha.116.303936 · Cited by 315 · see citing works
Direct Effect of Glucocorticoids on Lipolysis in Adipocytes
Xu, C., He, J., Jiang, H., Zu, L., Zhai, W., Pu, S., & Xu, G. (2009) · Molecular Endocrinology · doi:10.1210/me.2008-0464 · Cited by 291 · see citing works
Betaine chemistry, roles, and potential use in liver disease
Day, C. R., & Kempson, S. A. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.02.001 · Cited by 233 · see citing works
Adipogenic and lipolytic effects of chronic glucocorticoid exposure
Campbell, J. E., Peckett, A. J., D'souza, A. M., Hawke, T. J., & Riddell, M. C. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00045.2010 · Cited by 228 · see citing works
Wang, Z., Yao, T., Pini, M., Zhou, Z., Fantuzzi, G., & Song, Z. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00249.2009 · Cited by 153 · see citing works
Epigenetics in non-alcoholic fatty liver disease
Lee, J.-H., Kim, Y., Friso, S., & Choi, S. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.11.008 · Cited by 134 · see citing works
Regulation of triglyceride metabolism by glucocorticoid receptor
Wang, J.-C., Gray, N. E., Kuo, T., & Harris, C. A. (2012) · Cell & Bioscience · doi:10.1186/2045-3701-2-19 · Cited by 122 · see citing works
Wang, L.-J., Zhang, H.-W., Zhou, J.-Y., Liu, Y., Yang, Y., Chen, X.-L., Zhu, C.-H., Zheng, R.-D., Ling, W., & Zhu, H.-L. (2014) · Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2013.11.007 · Cited by 122 · see citing works
Epigenetic reprogramming in metabolic disorders: nutritional factors and beyond
Cheng, Z., Zheng, L., & Almeida, F. A. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.10.004 · Cited by 114 · see citing works
Wang, L., Chen, L., Tan, Y., Wei, J., Chang, Y., Jin, T., & Zhu, H. (2013) · Lipids in Health and Disease · doi:10.1186/1476-511x-12-34 · Cited by 109 · see citing works
Dexamethasone-induced autophagy mediates muscle atrophy through mitochondrial clearance
Troncoso, R., Paredes, F., Parra, V., Gatica, D., Vásquez-Trincado, C., Quiroga, C., Bravo, R., López‐Crisosto, C., Rodriguez, A. E., Oyarzún, A. P., et al. (2014) · Cell Cycle · doi:10.4161/cc.29272 · Cited by 108 · see citing works
Ge, C., Yu, R., Xu, M., Li, P., Fan, C., Li, J., & Kong, L. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.11.043 · Cited by 106 · see citing works
Kharbanda, K. K., Todero, S. L., King, A. L., Osna, N. A., McVicker, B. L., Tuma, D. J., Wisecarver, J. L., & Bailey, S. M. (2011) · International Journal of Hepatology · doi:10.1155/2012/962183 · Cited by 83 · see citing works
Cai, D., Jia, Y., Lu, J., Yuan, M., Sui, S., Song, H., & Zhao, R. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114514002402 · Cited by 83 · see citing works
Self-citationCai, D., Jia, Y., Song, H., Sui, S., Lu, J., Jiang, Z., & Zhao, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105504 · Cited by 73 · see citing works
Self-citationNonalcoholic steatohepatitis is associated with a state of betaine‐insufficiency
Sookoian, S., Puri, P., Castaño, G. O., Scian, R., Mirshahi, F., Sanyal, A. J., & Pirola, C. J. (2016) · Liver International · doi:10.1111/liv.13249 · Cited by 68 · see citing works
Liu, X., Wang, J., Li, R., Yang, X., Sun, Q., Albrecht, E., & Zhao, R. (2011) · Epigenetics · doi:10.4161/epi.6.7.16005 · Cited by 56 · see citing works
Self-citationChimin, P., de Farias, T. D. S. M., Torres‐Leal, F. L., Lopes, A. B., Campaña, A. B., Andreotti, S., & Lima, F. B. (2014) · Acta Physiologica · doi:10.1111/apha.12226 · Cited by 56 · see citing works
Dou, X., Xia, Y., Chen, J., Qian, Y., Li, S., Zhang, X., & Song, Z. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12765 · Cited by 50 · see citing works
Cai, D., Wang, J., Jia, Y., Liu, H., Yuan, M., Dong, H., & Zhao, R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.10.002 · Cited by 48 · see citing works
Self-citationThiazolidinediones attenuate lipolysis and ameliorate dexamethasone-induced insulin resistance
He, J., Xu, C. B., Kuang, J., Liu, Q., Jiang, H., Mo, L., Geng, B., & Xu, G. (2015) · Metabolism · doi:10.1016/j.metabol.2015.02.005 · Cited by 43 · see citing works
Airaksinen, K., Jokkala, J., Ahonen, I., Auriola, S. O. K., Kolehmainen, M., Hanhineva, K., & Tiihonen, K. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800455 · Cited by 42 · see citing works
Betaine reduces the expression of inflammatory adipokines caused by hypoxia in human adipocytes
Olli, K., Lahtinen, S. J., Rautonen, N., & Tiihonen, K. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512000888 · Cited by 39 · see citing works
Bingül, İ., Aydın, A., Başaran‐Küçükgergin, C., Doğan‐Ekici, I., Çoban, J., Doğru‐Abbasoğlu, S., & Uysal, M. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.07.028 · Cited by 38 · see citing works
Do, T. T. H., Garcia, M., Dalle, H., Dorothée, G., Moldes, M., Fève, B., & Buyse, M. (2018) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2018.08.010 · Cited by 38 · see citing works
Zhao, N., Yang, S., Jia, Y., Sun, B., He, B., & Zhao, R. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.12.003 · Cited by 37 · see citing works
Self-citationKuo, T., Chen, T.-C., Lee, R. A., Nguyen, N. H. T., Broughton, A. E., Zhang, D., & Wang, J.-C. (2017) · Diabetes · doi:10.2337/db16-0831 · Cited by 32 · see citing works
Xu, M., Che, L., Yang, Z., Zhang, P., Shi, J., Li, J., Lin, Y., Fang, Z., Che, L., Feng, B., et al. (2016) · Nutrients · doi:10.3390/nu8080498 · Cited by 30 · see citing works
Motta, K., Barbosa, A. M., Bobinski, F., Boschero, A. C., & Rafacho, A. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.09.024 · Cited by 27 · see citing works
Li, T., Guo, K., Qu, W., Han, Y., Wang, S., Lin, M., An, S., Li, X., Ma, S., Wang, T., et al. (2015) · Journal of Diabetes Investigation · doi:10.1111/jdi.12406 · Cited by 19 · see citing works
Kovačević, S., Brkljačić, J. M., Matić, G. M., & Elaković, I. (2016) · European Journal of Nutrition · doi:10.1007/s00394-016-1251-8 · Cited by 17 · see citing works
Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6 deficiency in rats
Kitagawa, E., Yamamoto, T., Fujishita, M., Ota, Y., Yamamoto, K., Nakagawa, T., & Hayakawa, T. (2016) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2016.1240604 · Cited by 17 · see citing works
Vanselow, J., Kucia, M., Langhammer, M., Koczan, D., & Metges, C. C. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-0906-1 · Cited by 7 · see citing works
Genome-Wide Analysis of Methylation in Bovine Clones by Methylated DNA Immunoprecipitation (MeDIP)
Kiefer, H. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1594-1_20 · Cited by 6 · see citing works
Flagged first, then by citations
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Arumugam, M. K., Paal, M. C., Donohue, T. M., Ganesan, M., Osna, N. A., & Kharbanda, K. K. (2021) · Biology · doi:10.3390/biology10060456 · Cited by 303 · see citing works
Effects of betaine on non-alcoholic liver disease
Chen, W., Xu, M., Xu, M., Wang, Y., Zou, Q.-Y., Xie, S., & Wang, L. (2021) · Nutrition Research Reviews · doi:10.1017/s0954422421000056 · Cited by 50 · see citing works
Theodorakis, N., Kreouzi, M., Pappas, A., & Nikolaou, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413438 · Cited by 43 · see citing works
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Li, Y., Jiang, W., Feng, Y. M., Wu, L., Jia, Y., & Zhao, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116263 · Cited by 37 · see citing works
Self-citationHao, J., Hu, H., Jiang, Z., Yu, X., Li, C., Chen, L., Xia, Y., Liu, D., & Wang, D. (2020) · Scientific Reports · doi:10.1038/s41598-020-61816-3 · Cited by 31 · see citing works
Jiao, P., Lu, H., Hao, L., Degen, A. A., Cheng, J., Yin, Z., Mao, S., & Xue, Y. (2024) · Nutrition Reviews · doi:10.1093/nutrit/nuae048 · Cited by 30 · see citing works
Wang, C., Li, M.-C., Huang, W., Huang, S., Wusiman, M., Liu, Z., & Zhu, H. (2025) · Theranostics · doi:10.7150/thno.102682 · Cited by 26 · see citing works
Wang, Y., Chen, J., Ji, Y., Lin, X., & Zhao, Y. (2021) · Animals · doi:10.3390/ani11123408 · Cited by 20 · see citing works
Fu, R., Liang, C., Chen, D., Tian, G., Zheng, P., He, J., Yu, J., Mao, X., Gu, Z., Yang, W., et al. (2023) · Journal of Animal Science · doi:10.1093/jas/skad080 · Cited by 9 · see citing works
Fu, R., Chen, D., Tian, G., Zheng, P., He, J., Yu, J., Mao, X., Huang, Z., Pu, J., & Yu, B. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105620 · Cited by 9 · see citing works
Ma, S., Wang, Y., Chen, L., Wang, W., Zhuang, X., Liu, Y., & Zhao, R. (2024) · Journal of Animal Science · doi:10.1093/jas/skae065 · Cited by 8 · see citing works
Self-citationMethyl donor micronutrients orchestrate lipid metabolism: The role of DNA methylation modification
Han, L., Tian, Q., Han, Q., Yin, Y., Yin, J. L., & Huang, X. (2024) · Journal of Integrative Agriculture · doi:10.1016/j.jia.2024.11.001 · Cited by 6 · see citing works
Exercise-mimicking effects of betaine in chronic disease prevention and management
Xu, Y., Gao, J., Wang, M., & Zhang, H. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1762908 · Cited by 3 · see citing works
Molecular Mechanism of Early-Life Chemical Exposure-Induced Harmful Effects
Wang, H., & Xu, D. (2020) · Springer eBooks · doi:10.1007/978-981-15-3797-4_13 · Cited by 2 · see citing works
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Xiao, H., & Liu, Y. (2024) · Springer eBooks · doi:10.1007/978-981-97-5730-5_10
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- Authors
- Zhao, N., Yang, S., Sun, B., Feng, Y., & Zhao, R.
- Affiliations
- Nanjing Agricultural University (CN)
- Corresponding author
- Zhao, Ruqian
- Venue
- European Journal of Nutrition
- Published
- 2019-06-14
- Volume
- 59
- Issue
- 4
- Pages
- 1707-1716
- ISSN
- 1436-6207 (ISSN-L)
- 1436-6215
- OpenAlex
- W2951615739
- Cited by
- 16
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China (2016YFD0500502)
- National Basic Research Program of China (2012CB124703)
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- adipose tissue, DNA methylation, adipose triglyceride lipase, HSL, dexamethasone, glucocorticoid receptor, promoter hypomethylation, inflammatory cytokines, corticosterone, maternal nutrition, offspring, pregnancy and lactation
- MeSH terms
- Adipose Tissue, Animals, Betaine, Female, Glucocorticoids, Lipolysis, Lipotropic Agents, Male, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Sprague-Dawley, DNA Methylation, Dietary Supplements, Protective Agents, Maternal Nutritional Physiological Phenomena, Rats
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