{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T09:50:43Z","timestamp":1783763443714,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":360,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2024R213"],"award-info":[{"award-number":["PNURSP2024R213"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Endocrinology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM), a metabolic disorder, has the hallmarks of persistent hyperglycemia, insulin resistance, and dyslipidemia. Protein\u2010tyrosine phosphatase 1B (PTP1B) was found to be overexpressed in many tissues in the case of T2DM and involved in the negative regulation of insulin signaling. So, PTP1B inhibition can act as a therapeutic target for T2DM. Numerous studies claimed the anti\u2010inflammatory, hypoglycemic, hepatoprotective, and hypolipidemic activities of <jats:italic>Dodonaea viscosa<\/jats:italic>. Previously, we generated the high\u2010fat diet (HFD)\u2010low dose streptozotocin (STZ)\u2013induced diabetic male mice model and treated it with a PTP1B inhibitor (5, 7\u2010dihydroxy\u20103, 6\u2010dimethoxy\u20102\u2010 (4\u2010methoxy\u20103\u2010 (3\u2010methyl\u20102\u2010enyl) phenyl)\u20104H\u2010chromen\u20104\u2010one), isolated from Dodonaea viscosa. In the current study, we aimed to investigate the De novo lipogenesis, adipocyte differentiation, augmentation of lipoproteins clearance, fatty acid uptake, antilipolysis activity, and hepatic steatosis of PTP1B inhibition in adipose and liver tissues of the HFD\u2010STZ\u2013induced diabetic mice model. We found the retrieval of normal morphology of adipocytes and hepatocytes in the compound\u2010treated group. The biochemical parameters showed the gradual reduction of LDL, VLDL, TC, and TG in the serum of the compound\u2010treated group. To further test our hypothesis, real\u2010time PCR was performed, and data revealed the reduction of PTP1B and other inflammatory markers in both tissues, showing enhanced expression of insulin signaling markers (INSR, IRS1, IRS2, and PI3K). Our compound upregulated the adipogenic (PPAR<jats:italic>\u03b3<\/jats:italic>), lipogenic (SREBP1c, FAS, ACC, and DGAT2), lipoprotein clearance (LPL, LDLR, and VLDLR), fatty acid uptake (CD36 and FATP1), and lipid droplet forming (FSP27 and perilipin\u20101) markers expressions in adipocytes and downregulated in hepatocytes. Furthermore, we found elevated cholesterol efflux (in adipose and liver) and decreased lipolysis in adipocytes and elevated in hepatocytes. Hence, we can conclude that our compound protects the adipocytes from abrupt lipolysis and stimulates adipocyte differentiation. In addition, it plays a hepatic protective role by shifting clearance and uptake of lipoproteins and fatty acids to the peripheral tissues and retrieving the fatty liver condition.<\/jats:p>","DOI":"10.1155\/ije\/3914332","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T07:04:42Z","timestamp":1735283082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Viscosol Treatment Ameliorates Insulin\u2010Mediated Regulation of Dyslipidemia, Hepatic Steatosis, and Lipid Metabolism by Targeting PTP1B in Type\u20102 Diabetic Mice Model"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0597-0343","authenticated-orcid":false,"given":"Idrees","family":"Raza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-4481","authenticated-orcid":false,"given":"Aamir","family":"Sohail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1427-5545","authenticated-orcid":false,"given":"Hamza","family":"Muneer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0088-8656","authenticated-orcid":false,"given":"Hajra","family":"Fayyaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zia","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany I.","family":"Almars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waheeb S.","family":"Aggad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailah M.","family":"Almohaimeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4259-2844","authenticated-orcid":false,"given":"Imran","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v6.i3.456"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1797-8"},{"key":"e_1_2_12_3_2","volume-title":"Diabetes Atlas","author":"Idf","year":"2021"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00514.2001"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.02.002"},{"key":"e_1_2_12_6_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/9781119436812.ch39","article-title":"Insulin-Mediated PI3K and AKT Signaling","author":"Kwon H.","year":"2020","journal-title":"Liver: Biology and Pathobiology"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.07.007"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213343109"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.9.1096"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0762-4"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-017-0189-z"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178672"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.02.018"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.193"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.08.004"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci41636"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203218109"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.04.118"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1097-2765(00)00137-4"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.80"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.10.241"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m800061200"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160920290"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.07.041"},{"key":"e_1_2_12_25_2","unstructured":"MuthukumranP. BegumandV. H. andPjijptrK. Anti-diabetic Activity of Dodonaea Viscosa (L) Leaf Extracts 2011."},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00040"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2323078"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280532"},{"key":"e_1_2_12_29_2","volume-title":"Henry\u2019s Clinical Diagnosis and Management by Laboratory Methods E-Book","author":"McPherson R. A.","year":"2021"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20110373"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-010-9206-3"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-12-407766-9.00017-1"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddstr.2005.05.002"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2019.11.004"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1474-8"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci200319451"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2007.08.004"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.142298199"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.8.2405"},{"key":"e_1_2_12_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.12.8026"},{"key":"e_1_2_12_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2013.05.006"},{"key":"e_1_2_12_42_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00367.2009"},{"key":"e_1_2_12_43_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.8.2442"},{"key":"e_1_2_12_44_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.m200466-jlr200"},{"key":"e_1_2_12_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m308522200"},{"key":"e_1_2_12_46_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34090"},{"key":"e_1_2_12_47_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1602"},{"key":"e_1_2_12_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.c800241200"},{"key":"e_1_2_12_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2014.02.007"},{"key":"e_1_2_12_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12184"},{"key":"e_1_2_12_51_2","unstructured":"Le SommerS. MartinaP. Martin-GranadosC. andDelibegovicM. Protein Tyrosine Phosphatase 1B (PTP1B) in the Immune System 2015."},{"key":"e_1_2_12_52_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m413240200"},{"key":"e_1_2_12_53_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0796"},{"key":"e_1_2_12_54_2","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0913"},{"key":"e_1_2_12_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401516101"},{"key":"e_1_2_12_56_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.20.6882"},{"key":"e_1_2_12_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosissup.2008.05.014"},{"key":"e_1_2_12_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086404"},{"key":"e_1_2_12_59_2","first-page":"1018","article-title":"Reduced Hepatic Expression of Adipose Tissue Triglyceride Lipase and CGI-58 May Contribute to the Development of Non-alcoholic Fatty Liver Disease in Patients With Insulin Resistance","volume":"43","author":"Kato M.","year":"2008","journal-title":"Journal of Gastroenterology and Hepatology"},{"key":"e_1_2_12_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26761"}],"container-title":["International Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ije\/3914332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T07:04:50Z","timestamp":1735283090000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ije\/3914332"}},"subtitle":[],"editor":[{"given":"Pamela","family":"Senesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1155\/ije\/3914332"],"URL":"https:\/\/doi.org\/10.1155\/ije\/3914332","archive":["Portico"],"relation":{},"ISSN":["1687-8337","1687-8345"],"issn-type":[{"value":"1687-8337","type":"print"},{"value":"1687-8345","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2023-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3914332"}}