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However, the role of Smad3 in dyslipidemia and non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes remains unclear, and whether targeting Smad3 has a therapeutic effect on these metabolic abnormalities remains unexplored. These topics were investigated in this study in Smad3 knockout (KO)-db\/db mice and by treating db\/db mice with a Smad3-specific inhibitor SIS3. Compared to Smad3 wild-type (WT)-db\/db mice, Smad3 KO-db\/db mice were protected against dyslipidemia and NAFLD. Similarly, treatment of db\/db mice with SIS3 at week 4 before the onset of type 2 diabetes until week 12 was capable of lowering blood glucose levels and improving diabetic dyslipidemia and NAFLD. In addition, using RNA-sequencing, the potential Smad3-target genes related to lipid metabolism was identified in the liver tissues of Smad3 KO\/WT mice, and the regulatory mechanisms were investigated. Mechanistically, we uncovered that Smad3 targeted peroxisome proliferator-activated receptor delta (PPAR\u03b4) to induce dyslipidemia and NAFLD in db\/db mice, which was improved by genetically deleting and pharmacologically inhibiting Smad3.<\/jats:p>","DOI":"10.3390\/ijms241411396","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:28:06Z","timestamp":1689294486000},"page":"11396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Smad3 Mediates Diabetic Dyslipidemia and Fatty Liver in db\/db Mice by Targeting PPAR\u03b4"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-3897","authenticated-orcid":false,"given":"Huijun","family":"He","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China"},{"name":"Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"},{"name":"Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6902-2732","authenticated-orcid":false,"given":"Yu","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-3736","authenticated-orcid":false,"given":"Patrick Ming-Kuen","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Translational Oncology, Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0737-3593","authenticated-orcid":false,"given":"Vivian Weiwen","family":"Xue","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Translational Oncology, Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaocui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-9411","authenticated-orcid":false,"given":"Jiaoyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoru","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-7954","authenticated-orcid":false,"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China"},{"name":"Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4283-9755","authenticated-orcid":false,"given":"Huiyao","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ecl.2022.02.011","article-title":"Dyslipidemia in Diabetes: When and How to Treat?","volume":"51","author":"Goldberg","year":"2022","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s40265-013-0023-5","article-title":"Dyslipidemia in type 2 diabetes: Prevalence, pathophysiology, and management","volume":"73","author":"Chehade","year":"2013","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e016947","DOI":"10.1161\/JAHA.120.016947","article-title":"Metabolic Dyslipidemia and Cardiovascular Outcomes in Type 2 Diabetes Mellitus: Findings from the Look AHEAD Study","volume":"10","author":"Kaze","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1161\/01.CIR.90.1.42","article-title":"Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild\/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin","volume":"90","author":"Hodis","year":"1994","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12933-021-01344-0","article-title":"CAPTURE: A multinational, cross-sectional study of cardiovascular disease prevalence in adults with type 2 diabetes across 13 countries","volume":"20","author":"Mosenzon","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000479874","article-title":"Crosstalk of Hyperglycemia and Dyslipidemia in Diabetic Kidney Disease","volume":"3","author":"Su","year":"2017","journal-title":"Kidney Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1001\/archinte.161.22.2685","article-title":"Total cholesterol\/HDL cholesterol ratio vs LDL cholesterol\/HDL cholesterol ratio as indices of ischemic heart disease risk in men: The Quebec Cardiovascular Study","volume":"161","author":"Lemieux","year":"2001","journal-title":"Arch. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12944-016-0270-z","article-title":"The triglyceride to high-density lipoprotein cholesterol (TG\/HDL-C) ratio as a predictor of insulin resistance but not of beta cell function in a Chinese population with different glucose tolerance status","volume":"15","author":"Zhou","year":"2016","journal-title":"Lipids Health Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2337\/dc10-2229","article-title":"Prevalence of and risk factors for hepatic steatosis and nonalcoholic Fatty liver disease in people with type 2 diabetes: The Edinburgh Type 2 Diabetes Study","volume":"34","author":"Williamson","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrgastro.2013.41","article-title":"Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis","volume":"10","author":"Anstee","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2337\/dc16-1787","article-title":"Management of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: A Call to Action","volume":"40","author":"Bril","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, H.L., Liu, T.T., and Lan, H.Y. (2021). TGF-Beta as a Master Regulator of Diabetic Nephropathy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157881"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.7150\/thno.51857","article-title":"Smad3 deficiency promotes beta cell proliferation and function in db\/db mice via restoring Pax6 expression","volume":"11","author":"Sheng","year":"2021","journal-title":"Theranostics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"154013","DOI":"10.1016\/j.metabol.2019.154013","article-title":"Deletion of Smad3 prevents renal fibrosis and inflammation in type 2 diabetic nephropathy","volume":"103","author":"Xu","year":"2020","journal-title":"Metabolism"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1111\/jcmm.16464","article-title":"Deletion of Smad3 protects against diabetic myocardiopathy in db\/db mice","volume":"25","author":"Dong","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.7150\/thno.67034","article-title":"Smad3 deficiency improves islet-based therapy for diabetes and diabetic kidney injury by promoting beta cell proliferation via the E2F3-dependent mechanism","volume":"12","author":"Wang","year":"2022","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"590","DOI":"10.2337\/db10-0403","article-title":"The protective role of Smad7 in diabetic kidney disease: Mechanism and therapeutic potential","volume":"60","author":"Chen","year":"2011","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5489","DOI":"10.7150\/ijbs.72977","article-title":"AANG Prevents Smad3-dependent Diabetic Nephropathy by Restoring Pancreatic beta-Cell Development in db\/db Mice","volume":"18","author":"Chung","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.2337\/db09-1631","article-title":"Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy","volume":"59","author":"Li","year":"2010","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nrendo.2016.135","article-title":"PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD","volume":"13","author":"Gross","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"F1032-47","DOI":"10.1152\/ajprenal.00152.2007","article-title":"PPARs and the kidney in metabolic syndrome","volume":"294","author":"Ruan","year":"2008","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.bbadis.2015.05.015","article-title":"Recent insights on the role of cholesterol in non-alcoholic fatty liver disease","volume":"1852","author":"Arguello","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, J., Montagner, A., Tan, N.S., and Wahli, W. (2018). Insights into the Role of PPARbeta\/delta in NAFLD. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071893"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"154342","DOI":"10.1016\/j.metabol.2020.154342","article-title":"Revealing the role of peroxisome proliferator-activated receptor beta\/delta in nonalcoholic fatty liver disease","volume":"114","author":"Zarei","year":"2021","journal-title":"Metabolism"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1074\/jbc.M110.138115","article-title":"Role of peroxisome proliferator-activated receptor {delta}\/{beta} in hepatic metabolic regulation","volume":"286","author":"Liu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41419-019-1458-8","article-title":"PPARdelta attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation","volume":"10","author":"Tong","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1194\/jlr.M046037","article-title":"PPARdelta activation attenuates hepatic steatosis in Ldlr-\/- mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity","volume":"55","author":"Bojic","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0092-8674(03)00269-1","article-title":"Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity","volume":"113","author":"Wang","year":"2003","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wagner, N., and Wagner, K.D. (2020). The Role of PPARs in Disease. Cells, 9.","DOI":"10.3390\/cells9112367"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Palomer, X., Barroso, E., Pizarro-Delgado, J., Pena, L., Botteri, G., Zarei, M., Aguilar, D., Montori-Grau, M., and Vazquez-Carrera, M. (2018). PPARbeta\/delta: A Key Therapeutic Target in Metabolic Disorders. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030913"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lange, N.F., Graf, V., Caussy, C., and Dufour, J.F. (2022). PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084305"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/nm1116","article-title":"Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy","volume":"10","author":"Cheng","year":"2004","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9609","DOI":"10.1074\/jbc.M212259200","article-title":"Transforming growth factor-beta inhibits adipocyte differentiation by Smad3 interacting with CCAAT\/enhancer-binding protein (C\/EBP) and repressing C\/EBP transactivation function","volume":"278","author":"Choy","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1038\/sj.emboj.7600437","article-title":"Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta\/delta expression","volume":"23","author":"Tan","year":"2004","journal-title":"EMBO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"464","DOI":"10.2337\/db10-0801","article-title":"Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet","volume":"60","author":"Tan","year":"2011","journal-title":"Diabetes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cmet.2011.04.013","article-title":"Protection from obesity and diabetes by blockade of TGF-beta\/Smad3 signaling","volume":"14","author":"Yadav","year":"2011","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.clinbiochem.2021.03.007","article-title":"Antioxidants other than vitamin C may be detected by glucose meters: Immediate relevance for patients with disorders targeted by antioxidant therapies","volume":"92","author":"Grzych","year":"2021","journal-title":"Clin. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3390\/biom5020472","article-title":"Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction","volume":"5","author":"Weidinger","year":"2015","journal-title":"Biomolecules"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.redox.2015.09.009","article-title":"Reciprocal regulation of TGF-beta and reactive oxygen species: A perverse cycle for fibrosis","volume":"6","author":"Liu","year":"2015","journal-title":"Redox Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.jhep.2013.01.011","article-title":"Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice","volume":"58","author":"Lin","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ko, B., and Van Raamsdonk, J.M. (2023). RNA Sequencing of Pooled Samples Effectively Identifies Differentially Expressed Genes. Biology, 12.","DOI":"10.3390\/biology12060812"},{"key":"ref_42","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\/14\/11396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:12:03Z","timestamp":1760127123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,13]]},"references-count":42,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411396"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411396","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,13]]}}}