{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T01:32:57Z","timestamp":1785202377287,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32002170"],"award-info":[{"award-number":["32002170"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["1610322023013"],"award-info":[{"award-number":["1610322023013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["25-LZIHPS-07"],"award-info":[{"award-number":["25-LZIHPS-07"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CARS-39-02"],"award-info":[{"award-number":["CARS-39-02"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["32002170"],"award-info":[{"award-number":["32002170"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["1610322023013"],"award-info":[{"award-number":["1610322023013"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["25-LZIHPS-07"],"award-info":[{"award-number":["25-LZIHPS-07"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["CARS-39-02"],"award-info":[{"award-number":["CARS-39-02"]}]},{"name":"Chinese Academy of Agricultural Sciences of Technology Innovation Project","award":["32002170"],"award-info":[{"award-number":["32002170"]}]},{"name":"Chinese Academy of Agricultural Sciences of Technology Innovation Project","award":["1610322023013"],"award-info":[{"award-number":["1610322023013"]}]},{"name":"Chinese Academy of Agricultural Sciences of Technology Innovation Project","award":["25-LZIHPS-07"],"award-info":[{"award-number":["25-LZIHPS-07"]}]},{"name":"Chinese Academy of Agricultural Sciences of Technology Innovation Project","award":["CARS-39-02"],"award-info":[{"award-number":["CARS-39-02"]}]},{"name":"Modern China Wool Cashmere Technology Research System","award":["32002170"],"award-info":[{"award-number":["32002170"]}]},{"name":"Modern China Wool Cashmere Technology Research System","award":["1610322023013"],"award-info":[{"award-number":["1610322023013"]}]},{"name":"Modern China Wool Cashmere Technology Research System","award":["25-LZIHPS-07"],"award-info":[{"award-number":["25-LZIHPS-07"]}]},{"name":"Modern China Wool Cashmere Technology Research System","award":["CARS-39-02"],"award-info":[{"award-number":["CARS-39-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heat stress is an important environmental factor affecting livestock production worldwide. Primary hepatocytes and preadipocytes derived from Hu sheep were used to establish a heat stress model. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that heat induction significantly increased the expression levels of heat stress protein (HSP) genes and the N6-methyladenosine (m6A) methylation modification genes: methyltransferase-like protein 3 (METTL3), methyltransferase-like protein 14 (METTL14), and fat mass and obesity associated protein (FTO). Heat stress simultaneously promoted cell apoptosis. Transcriptome sequencing identified 3980 upregulated genes and 2420 downregulated genes related to heat stress. A pathway enrichment analysis of these genes revealed significant enrichment in fatty acid biosynthesis, degradation, and the PI3K-Akt and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Overexpression of METTL3 in primary hepatocytes led to significant downregulation of HSP60, HSP70, and HSP110, and significantly increased mRNA m6A methylation; FTO interference generated the opposite results. Primary adipocytes showed similar results. Transcriptome analysis of cells under METTL3 (or FTO) inference and overexpression revealed differentially expressed genes enriched in the mitogen-activated protein kinase (MAPK) signaling pathways, as well as the PI3K-Akt and Ras signaling pathways. We speculate that METTL3 may increase the level of m6A methylation to inhibit fat deposition and\/or inhibit the expression of HSP genes to enhance the body\u2019s resistance to heat stress, while the FTO gene generated the opposite molecular mechanism. This study provides a scientific basis and theoretical support for sheep feeding and management practices during heat stress.<\/jats:p>","DOI":"10.3390\/ijms241511926","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:45:02Z","timestamp":1690332302000},"page":"11926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Molecular Mechanism of m6A Methylation Modification Genes METTL3 and FTO in Regulating Heat Stress in Sheep"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2625-0572","authenticated-orcid":false,"given":"Bowen","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6550-9236","authenticated-orcid":false,"given":"Jianbin","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohui","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-1083","authenticated-orcid":false,"given":"Zengkui","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s11356-021-15640-5","article-title":"Research on the evolution characteristics of future climate change in West Liao River Basin","volume":"29","author":"Zhao","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"348919","DOI":"10.4061\/2010\/348919","article-title":"Effects of Melatonin on Adrenal Cortical Functions of Indian Goats under Thermal Stress","volume":"2010","author":"Sejian","year":"2010","journal-title":"Vet. Med. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"820853","DOI":"10.3389\/fimmu.2021.820853","article-title":"Effects of Selenium as a Dietary Source on Performance, Inflammation, Cell Damage, and Reproduction of Livestock Induced by Heat Stress: A Review","volume":"12","author":"Zheng","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1007\/s00484-021-02167-0","article-title":"Negative relationship between dry matter intake and the temperature-humidity index with increasing heat stress in cattle: A global meta-analysis","volume":"65","author":"Harrison","year":"2021","journal-title":"Int. J. Biometeorol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/s41598-017-01120-9","article-title":"Heat Stress in Dairy Cattle Alters Lipid Composition of Milk","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41586-020-03135-1","article-title":"m6A RNA methylation regulates the fate of endogenous retroviruses","volume":"591","author":"Chelmicki","year":"2021","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/j.cell.2012.05.003","article-title":"Comprehensive analysis of mRNA methylation reveals enrichment in 3\u2032 UTRs and near stop codons","volume":"149","author":"Meyer","year":"2012","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/CM9.0000000000001528","article-title":"Development and validation of m6A RNA methylation regulators-based signature in lung adenocarcinoma","volume":"134","author":"Guo","year":"2021","journal-title":"Chin. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev-cellbio-100616-060758","article-title":"Rethinking m6A Readers, Writers, and Erasers","volume":"33","author":"Meyer","year":"2017","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12943-023-01782-2","article-title":"The role of m6A methylation in therapy resistance in cancer","volume":"22","author":"Zhuang","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_11","first-page":"9","article-title":"Dynamic transcriptomic m6A decoration: Writers, erasers, readers and functions in RNA metabolism","volume":"28","author":"Yang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nature15377","article-title":"Dynamic m6A mRNA methylation directs translational control of heat shock response","volume":"526","author":"Zhou","year":"2015","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2015.10.012","article-title":"5\u2032 UTR m6A Promotes Cap-Independent Translation","volume":"163","author":"Meyer","year":"2015","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s12192-018-00965-x","article-title":"The role of N6-methyladenosine RNA methylation in the heat stress response of sheep (Ovis aries)","volume":"24","author":"Lu","year":"2019","journal-title":"Cell Stress Chaperones"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lu, Z., Chu, M., Li, Q., Jin, M., Fei, X., Ma, L., Zhang, L., and Wei, C. (2019). Transcriptomic Analysis Provides Novel Insights into Heat Stress Responses in Sheep. Animals, 9.","DOI":"10.3390\/ani9060387"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.3390\/cimb44080248","article-title":"Development of an Improved Method for the Isolation and Culture of Newborn Sheep Primary Hepatocytes","volume":"44","author":"Chen","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yu, J., Li, Y., Wang, T., and Zhong, X. (2018). Modification of N6-methyladenosine RNA methylation on heat shock protein expression. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198604"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C1058","DOI":"10.1152\/ajpcell.2000.279.4.C1058","article-title":"Intra- and extracellular measurement of reactive oxygen species produced during heat stress in diaphragm muscle","volume":"279","author":"Zuo","year":"2000","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s12192-021-01201-9","article-title":"Heat stress promotes lipid accumulation by inhibiting the AMPK-PGC-1\u03b1 signaling pathway in 3T3-L1 preadipocytes","volume":"26","author":"Huang","year":"2021","journal-title":"Cell Stress Chaperones"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.2527\/jas.2015-9074","article-title":"Heat stress enhances adipogenic differentiation of subcutaneous fat depot-derived porcine stromovascular cells","volume":"93","author":"Qu","year":"2015","journal-title":"J. Anim. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1093\/jas\/skz271","article-title":"Hypertrophic muscle growth and metabolic efficiency were impaired by chronic heat stress, improved by zilpaterol supplementation, and not affected by ractopamine supplementation in feedlot lambs1","volume":"97","author":"Barnes","year":"2019","journal-title":"J. Anim. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jtherbio.2019.07.007","article-title":"Benefits of the inclusion of a\u00e7ai oil in the diet of dairy sheep in heat stress on health and milk production and quality","volume":"84","author":"Klauck","year":"2019","journal-title":"J. Therm. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.meatsci.2016.02.024","article-title":"Effects of chestnut tannins on the meat quality, welfare, and antioxidant status of heat-stressed lambs","volume":"116","author":"Liu","year":"2016","journal-title":"Meat Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s40104-022-00783-3","article-title":"Heat stress in pigs and broilers: Role of gut dysbiosis in the impairment of the gut-liver axis and restoration of these effects by probiotics, prebiotics and synbiotics","volume":"13","author":"Ringseis","year":"2022","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature12730","article-title":"N6-methyladenosine-dependent regulation of messenger RNA stability","volume":"505","author":"Wang","year":"2014","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"935939","DOI":"10.3389\/fvets.2022.935939","article-title":"Rumen-protected zinc-methionine dietary inclusion alters dairy cow performances, and oxidative and inflammatory status under long-term environmental heat stress","volume":"9","author":"Kargar","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.tig.2019.12.007","article-title":"Molecular Mechanisms Driving mRNA Degradation by m6A Modification","volume":"36","author":"Lee","year":"2020","journal-title":"Trends Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Horodyska, J., Wimmers, K., Reyer, H., Trakooljul, N., Mullen, A.M., Lawlor, P.G., and Hamill, R.M. (2018). RNA-seq of muscle from pigs divergent in feed efficiency and product quality identifies differences in immune response, growth, and macronutrient and connective tissue metabolism. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5175-y"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Khan, S., Wu, S.-B., and Roberts, J. (2019). RNA-sequencing analysis of shell gland shows differences in gene expression profile at two time-points of eggshell formation in laying chickens. BMC Genom., 20.","DOI":"10.1186\/s12864-019-5460-4"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Salleh, S.M., Mazzoni, G., L\u00f8vendahl, P., and Kadarmideenco, H.N. (2018). Gene expression networks from RNA sequencing of dairy cattle identifies genes and pathways affecting feed efficiency. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2553-z"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1146\/annurev-genom-091416-035332","article-title":"Cognitive Dysfunctions in Intellectual Disabilities: The Contributions of the Ras-MAPK and PI3K-AKT-mTOR Pathways","volume":"18","author":"Borrie","year":"2017","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2009.12.043","article-title":"Rap1, a mercenary among the Ras-like GTPases","volume":"340","author":"Frische","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1083\/jcb.201710161","article-title":"Desmoplakin maintains gap junctions by inhibiting Ras\/MAPK and lysosomal degradation of connexin-43","volume":"217","author":"Kam","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.biopha.2018.03.124","article-title":"Inhibitory effect of sinigrin on adipocyte differentiation in 3T3-L1 cells: Involvement of AMPK and MAPK pathways","volume":"102","author":"Lee","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ejphar.2016.12.006","article-title":"Epigallocatechin-3-gallate inhibits adipogenesis through down-regulation of PPAR\u03b3 and FAS expression mediated by PI3K-AKT signaling in 3T3-L1 cells","volume":"795","author":"Wu","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3389\/fimmu.2016.00171","article-title":"Heat Shock Protein-Peptide and HSP-Based Immunotherapies for the Treatment of Cancer","volume":"7","author":"Shevtsov","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Choi, R.-Y., and Lee, M.-K. (2021). Polygonum multiflorum Thunb. Hot Water Extract Reverses High-Fat Diet-Induced Lipid Metabolism of White and Brown Adipose Tissues in Obese Mice. Plants, 10.","DOI":"10.3390\/plants10081509"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"985040","DOI":"10.3389\/fvets.2023.985040","article-title":"COPA3 peptide supplementation alleviates the heat stress of chicken fibroblasts","volume":"10","author":"Siddiqui","year":"2023","journal-title":"Front. Vet. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7529","DOI":"10.1096\/fj.201802644R","article-title":"METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1\/STAT5\/C\/EBP\u03b2 pathway via an m6A-YTHDF2-dependent manner","volume":"33","author":"Yao","year":"2019","journal-title":"FASEB J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1016\/j.celrep.2018.10.068","article-title":"Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation","volume":"25","author":"Zhong","year":"2018","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2001563","DOI":"10.1002\/advs.202001563","article-title":"Novel Insights into Adipogenesis from the Perspective of Transcriptional and RNA N6-Methyladenosine-Mediated Post-Transcriptional Regulation","volume":"7","author":"Song","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1080\/15548627.2019.1659617","article-title":"m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7","volume":"16","author":"Wang","year":"2020","journal-title":"Autophagy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s00484-021-02083-3","article-title":"Impacts of heat stress on immune responses and oxidative stress in farm animals and nutritional strategies for amelioration","volume":"65","author":"Chauhan","year":"2021","journal-title":"Int. J. Biometeorol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, D., Zhao, Z., Shi, Y., Luo, J., Chen, T., Xi, Q., Zhang, Y., and Sun, J. (2022). CircEZH2 Regulates Milk Fat Metabolism through miR-378b Sponge Activity. Animals, 12.","DOI":"10.3390\/ani12060718"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yin, C., Tang, S., Liu, L., Cao, A., Xie, J., and Zhang, H. (2021). Effects of Bile Acids on Growth Performance and Lipid Metabolism during Chronic Heat Stress in Broiler Chickens. Animals, 11.","DOI":"10.3390\/ani11030630"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"877178","DOI":"10.3389\/fphys.2022.877178","article-title":"Betaine Regulates the Production of Reactive Oxygen Species through Wnt10b Signaling in the Liver of Zebrafish","volume":"13","author":"Li","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Dunshea, F.R., Oluboyede, K., DiGiacomo, K., Leury, B.J., and Cottrell, J.J. (2019). Betaine Improves Milk Yield in Grazing Dairy Cows Supplemented with Concentrates at High Temperatures. Animals, 9.","DOI":"10.3390\/ani9020057"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s40104-022-00795-z","article-title":"m6A demethylase FTO regulate CTNNB1 to promote adipogenesis of chicken preadipocyte","volume":"13","author":"Li","year":"2022","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.jnutbio.2015.08.014","article-title":"The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase \u03b11 subunit","volume":"26","author":"Zhou","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/11926\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:18:50Z","timestamp":1760127530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/11926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,25]]},"references-count":51,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241511926"],"URL":"https:\/\/doi.org\/10.3390\/ijms241511926","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,25]]}}}