{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:03:13Z","timestamp":1789502593471,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004252","name":"Qatar University H3P","doi-asserted-by":"publisher","award":["QPH3P-BRC-2021-451"],"award-info":[{"award-number":["QPH3P-BRC-2021-451"]}],"id":[{"id":"10.13039\/501100004252","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Impaired adipogenesis is associated with the development of insulin resistance and an increased risk of type 2 diabetes (T2D). GATA Binding Protein 3 (GATA3) is implicated in impaired adipogenesis and the onset of insulin resistance. Therefore, we hypothesize that inhibition of GATA3 could promote adipogenesis, restore healthy fat distribution, and enhance insulin signaling. Primary human preadipocytes were treated with GATA3 inhibitor (DNAzyme hgd40). Cell proliferation, adipogenic capacity, gene expression, and insulin signaling were measured following well-established protocols. BALB\/c mice were treated with DNAzyme hgd40 over a period of 2 weeks. Liposomes loaded with DNAzyme hgd40, pioglitazone (positive), or vehicle (negative) controls were administered subcutaneously every 2 days at the right thigh. At the end of the study, adipose tissues were collected and weighed from the site of injection, the opposite side, and the omental depot. Antioxidant enzyme (superoxide dismutase and catalase) activities were assessed in animals\u2019 sera, and gene expression was measured using well-established protocols. In vitro GATA3 inhibition induced the adipogenesis of primary human preadipocytes and enhanced insulin signaling through the reduced expression of p70S6K. In vivo GATA3 inhibition promoted adipogenesis at the site of injection and reduced MCP-1 expression. GATA3 inhibition also reduced omental tissue size and PPAR\u03b3 expression. These findings suggest that modulating GATA3 expression offers a potential therapeutic benefit by correcting impaired adipogenesis, promoting healthy fat distribution, improving insulin sensitivity, and potentially lowering the risk of T2D.<\/jats:p>","DOI":"10.3390\/ijms231911142","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T21:10:05Z","timestamp":1663881005000},"page":"11142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity"],"prefix":"10.3390","volume":"23","author":[{"given":"Hend","family":"Al-Jaber","sequence":"first","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nura A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Govindharajan","sequence":"additional","affiliation":[{"name":"Laboratory Research Animal Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1087-5962","authenticated-orcid":false,"given":"Samir","family":"Taha","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery, Al-Wakra Hospital, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-9260","authenticated-orcid":false,"given":"Jomon","family":"John","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery, Al-Wakra Hospital, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharique","family":"Halim","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery, Al-Wakra Hospital, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Alser","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamma","family":"Al-Muraikhy","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7263-4905","authenticated-orcid":false,"given":"Najeha Rizwana","family":"Anwardeen","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-1582","authenticated-orcid":false,"given":"Abdelali","family":"Agouni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelbary","family":"Elhissi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamda A.","family":"Al-Naemi","sequence":"additional","affiliation":[{"name":"Laboratory Research Animal Center, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layla","family":"Al-Mansoori","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3803-4604","authenticated-orcid":false,"given":"Mohamed A.","family":"Elrayess","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.2337\/diacare.21.9.1414","article-title":"Global burden of diabetes, 1995\u20132025: Prevalence, numerical estimates, and projections","volume":"21","author":"King","year":"1998","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3810\/pgm.2009.11.2074","article-title":"The medical risks of obesity","volume":"121","year":"2009","journal-title":"Postgrad. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1055\/s-0029-1192044","article-title":"Adipose tissue dysfunction in obesity","volume":"117","author":"Bluher","year":"2009","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G.A., Beguinot, F., and Miele, C. (2019). Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092358"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.molimm.2012.01.005","article-title":"Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans","volume":"50","author":"Goossens","year":"2012","journal-title":"Mol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ambele, M.A., Dhanraj, P., Giles, R., and Pepper, M.S. (2020). Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124283"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(11)60679-X","article-title":"National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2\u00b77 million participants","volume":"378","author":"Danaei","year":"2011","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"758","DOI":"10.7326\/0003-4819-159-11-201312030-00008","article-title":"Are metabolically healthy overweight and obesity benign conditions?: A systematic review and meta-analysis","volume":"159","author":"Kramer","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"699","DOI":"10.2337\/diabetes.47.5.699","article-title":"The metabolically obese, normal-weight individual revisited","volume":"47","author":"Ruderman","year":"1998","journal-title":"Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.cmet.2011.07.015","article-title":"Insulin resistance, hyperglycemia, and atherosclerosis","volume":"14","author":"Bornfeldt","year":"2011","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1007\/s00125-007-0790-1","article-title":"Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance","volume":"50","author":"Adiels","year":"2007","journal-title":"Diabetologia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2337\/diacare.14.3.173","article-title":"Insulin Resistance: A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease","volume":"14","author":"Ferrannini","year":"1991","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"O\u2019Connell, J., Lynch, L., Cawood, T.J., Kwasnik, A., Nolan, N., Geoghegan, J., McCormick, A., O\u2019Farrelly, C., and O\u2019Shea, D. (2010). The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009997"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mce.2009.11.011","article-title":"The autocrine and paracrine roles of adipokines","volume":"318","author":"Karastergiou","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1161\/ATVBAHA.107.147835","article-title":"Inflamed adipose tissue: A culprit underlying the metabolic syndrome and atherosclerosis","volume":"27","author":"Gustafson","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nrm2066","article-title":"Adipocyte differentiation from the inside out","volume":"7","author":"Rosen","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1007\/s00125-016-4031-3","article-title":"Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance","volume":"59","author":"Almuraikhy","year":"2016","journal-title":"Diabetologia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1126\/science.290.5489.134","article-title":"Function of GATA transcription factors in preadipocyte-adipocyte transition","volume":"290","author":"Tong","year":"2000","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1128\/MCB.25.2.706-715.2005","article-title":"Interaction between GATA and the C\/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation","volume":"25","author":"Tong","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1002\/j.1460-2075.1995.tb00147.x","article-title":"Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153)","volume":"14","author":"Batchvarova","year":"1995","journal-title":"EMBO J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11432","DOI":"10.1074\/jbc.M411741200","article-title":"Delta-interacting protein A, a new inhibitory partner of CCAAT\/enhancer-binding protein beta, implicated in adipocyte differentiation","volume":"280","author":"Bezy","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9863","DOI":"10.1128\/MCB.24.22.9863-9872.2004","article-title":"ETO\/MTG8 is an inhibitor of C\/EBPbeta activity and a regulator of early adipogenesis","volume":"24","author":"Rochford","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/sj.embor.embor805","article-title":"A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells","volume":"4","author":"Shi","year":"2003","journal-title":"EMBO Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1358\/dnp.2003.16.9.829340","article-title":"GATA transcription factors and fat cell formation","volume":"16","author":"Tong","year":"2003","journal-title":"Drug News Perspect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/eji.201646450","article-title":"GATA-3-specific DNAzyme\u2014A novel approach for stratified asthma therapy","volume":"47","author":"Garn","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.2337\/diabetes.50.8.1863","article-title":"Effects of Pioglitazone on Adipose Tissue Remodeling Within the Setting of Obesity and Insulin Resistance","volume":"50","author":"Eckhardt","year":"2001","journal-title":"Diabetes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109735","DOI":"10.1016\/j.cellsig.2020.109735","article-title":"Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes","volume":"75","author":"Madani","year":"2020","journal-title":"Cell Signal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.2337\/diabetes.48.11.2210","article-title":"Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women","volume":"48","author":"Dvorak","year":"1999","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Al-Sulaiti, H., D\u00f6mling, A.S., and Elrayess, M.A.M. (2019). Mediators of Impaired Adipogenesis in Obesity-Associated Insulin Resistance and T2DM. Adipose Tissue\u2014An Update, IntechOpen. Chapter 7.","DOI":"10.5772\/intechopen.88746"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2174\/1573399816666200705210417","article-title":"GATA-3 as a Potential Therapeutic Target for Insulin Resistance and Type 2 Diabetes Mellitus","volume":"17","author":"Elrayess","year":"2021","journal-title":"Curr. Diabetes Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1210\/jcem.87.6.8567","article-title":"Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients","volume":"87","author":"Miyazaki","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1161\/01.RES.0000099243.20096.FA","article-title":"Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis","volume":"93","author":"Fukumura","year":"2003","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e65996","DOI":"10.7554\/eLife.65996","article-title":"Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease","volume":"10","author":"Vendrell","year":"2021","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.tem.2014.04.001","article-title":"PPARgamma and the global map of adipogenesis and beyond","volume":"25","author":"Lefterova","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35375","DOI":"10.1074\/jbc.M806480200","article-title":"S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-\u03b1 signaling through IKK2","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.soard.2010.05.013","article-title":"Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity","volume":"7","author":"Hardy","year":"2011","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1179\/135100009X392467","article-title":"Expression of extracellular superoxide dismutase during adipose differentiation in 3T3-L1 cells","volume":"14","author":"Adachi","year":"2009","journal-title":"Redox Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"E999","DOI":"10.1152\/ajpendo.00377.2009","article-title":"Inflammation and impaired adipogenesis in hypertrophic obesity in man","volume":"297","author":"Gustafson","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cyto.2012.06.018","article-title":"Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes","volume":"60","author":"Panee","year":"2012","journal-title":"Cytokine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1073\/pnas.1133870100","article-title":"Monocyte chemoattractant protein 1 in obesity and insulin resistance","volume":"100","author":"Sartipy","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12967-018-1548-x","article-title":"Triglyceride profiling in adipose tissues from obese insulin sensitive, insulin resistant and type 2 diabetes mellitus individuals","volume":"16","author":"Diboun","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1080\/08982104.2016.1259628","article-title":"Ethanol-based proliposome delivery systems of paclitaxel for in vitro application against brain cancer cells","volume":"28","author":"Najlah","year":"2018","journal-title":"J. Liposome Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gayoso-Diz, P., Otero-Gonz\u00e1lez, A., Rodriguez-Alvarez, M.X., Gude, F., Garc\u00eda, F., De Francisco, A., and Quintela, A.G. (2013). Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: Effect of gender and age: EPIRCE cross-sectional study. BMC Endocr. Disord., 13.","DOI":"10.1186\/1472-6823-13-47"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/1753-0407.12913","article-title":"Diabetes in developing countries","volume":"11","author":"Misra","year":"2019","journal-title":"J. Diabetes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.freeradbiomed.2017.01.015","article-title":"4-hydroxynonenal causes impairment of human subcutaneous adipogenesis and induction of adipocyte insulin resistance","volume":"104","author":"Elrayess","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:37:20Z","timestamp":1760143040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":46,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911142"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911142","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]}}}