{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:47:22Z","timestamp":1793677642521,"version":"4.5.1"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The exact link between obesity, vitamin D deficiency, and their relation to cellular senescence in the pathogenesis of subclinical atherosclerosis is still under debate. Therefore, the current study aims to verify the possible role of vitamin D deficiency and cellular senescence in the pathogenesis of obesity-related subclinical atherosclerosis. Moreover, it aims to investigate the possible protective role of vitamin D supplementation. Fifty-seven male albino rats were enrolled in the study and classified into four groups: negative (10) and positive control groups (10), an obese model group (24), and a vitamin-D-supplemented obese group (13). Aortic tissue samples and fasting blood samples were collected. The following biochemical investigations were performed: serum cholesterol, triglycerides, HDL-C, LDL-C, ALT, AST, CPK, CK-MB, and hs-cTnt. HOMA-IR was calculated. Moreover, serum SMP-30, 25 (OH)Vitamin D3, and eNOS were determined by the ELISA technique. Aortic gene expression of eNOS, SMP-30, and P53 was estimated by real-time qRT-PCR. Serum 25(OH) D3 and SMP-30 were lower in the obese group. In addition, the obese group showed higher serum lipid profile, HOMA-IR, eNOS, ALT, AST, CPK, CK-MB, and hs-cTnt than the control groups, while decreased levels were found in the vitamin-D-treated obese group. Gene expression of eNOS and SMP-30 were in accordance with their serum levels. A positive correlation was found between vitamin D level and SMP-30. In conclusion, obesity is associated with vitamin D deficiency and enhanced cellular senescence. They could play a role in the pathogenesis of obesity-associated subclinical atherosclerosis and endothelial dysfunction. Vitamin D supplements could play a protective role against such obesity-related comorbidity.<\/jats:p>","DOI":"10.3390\/cells10040920","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T10:20:11Z","timestamp":1618568411000},"page":"920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cellular Senescence and Vitamin D Deficiency Play a Role in the Pathogenesis of Obesity-Associated Subclinical Atherosclerosis: Study of the Potential Protective Role of Vitamin D Supplementation"],"prefix":"10.3390","volume":"10","author":[{"given":"Abdulhadi I.","family":"Bima","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah S.","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayza F.","family":"Al Fayez","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taghreed M.","family":"Khawaja","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-2723","authenticated-orcid":false,"given":"Salwa M.","family":"Abo El-Khair","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-6184","authenticated-orcid":false,"given":"Ayman Z.","family":"Elsamanoudy","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia"},{"name":"Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2000). Obesity: Preventing and Managing the Global Epidemic, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/MCO.0b013e328312c37d","article-title":"Sarcopenic obesity: Definition, cause, and consequences","volume":"11","author":"Ferrucci","year":"2008","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Engin, A. (2017). The definition and prevalence of obesity and metabolic syndrome. Obesity and Lipotoxicity, Springer.","DOI":"10.1007\/978-3-319-48382-5_1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/MED.0000000000000212","article-title":"Current Opinion in Endocrinology, Diabetes, and Obesity \u201cPituitary gigantism: Update on Molecular Biology and Management\u201d","volume":"23","author":"Lodish","year":"2016","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.autrev.2013.02.004","article-title":"Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia, and mortality\u2014A review of recent evidence","volume":"12","author":"Pludowski","year":"2013","journal-title":"Autoimmun. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1083\/jcb.201009094","article-title":"Four faces of cellular senescence for faces of senescence","volume":"192","author":"Rodier","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_7","first-page":"168","article-title":"Cellular Senescence: What, Why, and How","volume":"29","author":"Regulski","year":"2017","journal-title":"Wounds Compend. Clin. Res. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10522-018-9763-7","article-title":"Obesity and type-2 diabetes as inducers of premature cellular senescence and aging","volume":"19","author":"Burton","year":"2018","journal-title":"Biogerontology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Singh, S.S., Pilkerton, C.S., Shrader, C.D., and Frisbee, S.J. (2018). Subclinical atherosclerosis, cardiovascular health, and disease risk: Is there a case for the Cardiovascular Health Index in the primary prevention population?. BMC Public Health, 18.","DOI":"10.1186\/s12889-018-5263-6"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/eurheartj\/ehs174","article-title":"The intriguing metabolically healthy but obese phenotype: Cardiovascular prognosis and role of fitness","volume":"34","author":"Ortega","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1016\/j.ijcard.2013.06.151","article-title":"Vitamin D serum levels are associated with cardiovascular outcome in coronary artery disease","volume":"168","author":"Siasos","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ijcard.2011.01.032","article-title":"Vitamin D deficiency is associated with significant coronary stenoses in asymptomatic African American chronic cocaine users","volume":"158","author":"Lai","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1016\/j.jacc.2016.03.530","article-title":"Short telomere load, telomere length, and subclinical atherosclerosis: The PESA study","volume":"67","author":"Fuster","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1258\/002367707779399518","article-title":"Anthropometrical parameters and markers of obesity in rats","volume":"41","author":"Novelli","year":"2007","journal-title":"Lab. Anim."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Farhangi, M.A., Mesgari-Abbasi, M., Nameni, G., Hajiluian, G., and Shahabi, P. (2017). The effects of vitamin D administration on brain inflammatory markers in high-fat diet-induced obese rats. BMC Neurosci., 18.","DOI":"10.1186\/s12868-017-0400-1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_17","first-page":"1079","article-title":"Effects of ginsenoside Rb1 on oxidative stress injury in rat spinal cords by regulating the eNOS\/Nrf2\/HO-1 signaling pathway","volume":"16","author":"Liu","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_18","first-page":"10853","article-title":"Anti-senescence role of coenzyme Q10 and 17 \u03b2-estradiol on submandibular gland of ovariectomized rats: Histological, immunohistological and molecular studies","volume":"9","author":"Arafat","year":"2016","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2131\/jts.36.191","article-title":"Cadmium toxicity is caused by accumulation of p53 through the down-regulation of Ube2d family genes in vitro and in vivo","volume":"36","author":"Tokumoto","year":"2011","journal-title":"J. Toxicol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"604275","DOI":"10.1155\/2015\/604275","article-title":"A novel rat model of vitamin D deficiency: Safe and rapid induction of vitamin D and calcitriol deficiency without hyperparathyroidism","volume":"2015","author":"Stavenuiter","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"838","DOI":"10.2174\/1871530319666190122094039","article-title":"25 Hydroxyvitamin D Levels are Negatively and Independently Associated with Fat Mass in a Cohort of Healthy Overweight and Obese Subjects","volume":"19","author":"Martino","year":"2019","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1017\/S0007114517000320","article-title":"Vitamin D deficiency and sufficiency among Canadian children residing at high latitude following the revision of the RDA of vitamin D intake in 2010","volume":"117","author":"Munasinghe","year":"2017","journal-title":"Br. J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.15690\/vsp.v13i6.1198","article-title":"Vitamin D insufficiency in children of tender years in Russia: The results of a multi-center cohort study Rodnichok (2013\u20132014)","volume":"13","author":"Zakharova","year":"2014","journal-title":"Curr. Pediatrics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s00198-011-1606-1","article-title":"High prevalence of vitamin D deficiency among healthy Saudi Arabian men: Relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors","volume":"23","author":"Ardawi","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/IJBCRR\/2016\/30221","article-title":"Study of the Possible Effect of Obesity on Vitamin D Level among a Sample of Adult Men in the Western Region of Kingdom of Saudi Arabia","volume":"14","author":"Elsamanoudy","year":"2016","journal-title":"Int. J. Biochem. Res. Rev."},{"key":"ref_26","first-page":"801","article-title":"Serum 25 (OH) D and lipid levels in Chinese obese and normal-weight males before and after oral vitamin D supplementation","volume":"26","author":"Zhou","year":"2013","journal-title":"Biomed. Environ. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/MED.0000000000000371","article-title":"Vitamin D in obesity","volume":"24","author":"Walsh","year":"2017","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/jbmr.2979","article-title":"Vitamin D storage in adipose tissue of obese and normal weight women","volume":"32","author":"Carrelli","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/MCO.0000000000000315","article-title":"Changes in circulating vitamin D levels with loss of adipose tissue","volume":"19","author":"Gangloff","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9488","DOI":"10.3748\/wjg.v22.i43.9488","article-title":"Nonalcoholic fatty liver disease\u2014A multisystem disease?","volume":"22","author":"Mikolasevic","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Vranic, L., Mikolasevic, I., and Milic, S. (2019). Vitamin D Deficiency: Consequence or Cause of Obesity?. Medicina, 55.","DOI":"10.3390\/medicina55090541"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s13679-015-0176-5","article-title":"Causes of vitamin D deficiency and effect of vitamin D supplementation on metabolic complications in obesity: A review","volume":"4","author":"Wamberg","year":"2015","journal-title":"Curr. Obes. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.numecd.2012.04.013","article-title":"Serum 25-hydroxyvitamin D levels, obesity and the metabolic syndrome among Korean children","volume":"23","author":"Lee","year":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E4556","DOI":"10.1073\/pnas.1506954112","article-title":"Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities","volume":"112","author":"Chen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1515\/cclm-2014-1184","article-title":"The role of telomeres and vitamin D in cellular aging and age-related diseases","volume":"53","author":"Pusceddu","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6825","DOI":"10.1113\/JP274887","article-title":"Vitamin D deficiency accelerates ageing and age-related diseases: A novel hypothesis","volume":"595","author":"Berridge","year":"2017","journal-title":"J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s11657-016-0297-9","article-title":"Vitamin D deficiency in older adults and its associated factors: A cross-sectional analysis of the Mexican Health and Aging Study","volume":"12","year":"2017","journal-title":"Arch. Osteoporos."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.neubiorev.2016.06.040","article-title":"Mitochondrial dysfunction in bipolar disorder: Evidence, pathophysiology and translational implications","volume":"68","author":"Scaini","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_39","first-page":"921348","article-title":"Possible role of hyperinsulinemia and insulin resistance in lower vitamin D levels in overweight and obese patients","volume":"2013","author":"Nitti","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1038\/s41593-019-0505-1","article-title":"Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence","volume":"22","author":"Chow","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3407306","DOI":"10.1155\/2018\/3407306","article-title":"The impact of obesity on the cardiovascular system","volume":"2018","author":"Csige","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"342","DOI":"10.5551\/jat.50633","article-title":"Relationships of Obesity-Related Indices and Metabolic Syndrome with Subclinical Atherosclerosis in Middle-Aged Untreated Japanese Workers","volume":"27","author":"Sugiura","year":"2020","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1161\/CIRCULATIONAHA.110.005264","article-title":"Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study","volume":"123","author":"Saunders","year":"2011","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jchf.2014.05.017","article-title":"Obesity, subclinical myocardial injury, and incident heart failure","volume":"2","author":"Ndumele","year":"2014","journal-title":"JACC Heart Fail."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/RUQ.0000000000000386","article-title":"Assessment of Subclinical Atherosclerosis in Vitamin D Deficiency","volume":"35","author":"Aydin","year":"2019","journal-title":"Ultrasound Q."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.atherosclerosis.2012.12.013","article-title":"Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes","volume":"227","author":"Yiu","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_47","first-page":"67","article-title":"Association between serum vitamin D levels and subclinical coronary atherosclerosis and plaque burden\/composition in young adult population","volume":"15","author":"Satilmis","year":"2015","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1681\/ASN.V133621","article-title":"Synthesis of 1, 25-dihydroxyvitamin D3 by human endothelial cells is regulated by inflammatory cytokines: A novel autocrine determinant of vascular cell adhesion","volume":"13","author":"Zehnder","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jacc.2011.02.051","article-title":"Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans","volume":"58","author":"Patel","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1161\/CIRCULATIONAHA.109.856070","article-title":"1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus","volume":"120","author":"Oh","year":"2009","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fcvm.2018.00018","article-title":"Vascular senescence in cardiovascular and metabolic diseases","volume":"5","author":"Katsuumi","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"598","DOI":"10.5114\/aoms.2018.75864","article-title":"Effects of vitamin D supplementation on insulin resistance and dyslipidemia in overweight and obese premenopausal women","volume":"15","author":"Imga","year":"2019","journal-title":"Arch. Med. Sci. AMS"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e12951","DOI":"10.1111\/acel.12951","article-title":"1, 25-Dihydroxyvitamin D exerts an antiaging role by activation of Nrf2-antioxidant signaling and inactivation of p16\/p53-senescence signaling","volume":"18","author":"Chen","year":"2019","journal-title":"Aging Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.2147\/CIA.S141265","article-title":"Vascular aging and subclinical atherosclerosis: Why such a \u201cnever ending\u201d and challenging story in cardiology?","volume":"12","author":"Iurciuc","year":"2017","journal-title":"Clin. Interv. Aging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"732","DOI":"10.5114\/aoms.2017.68237","article-title":"Vitamin D deficiency and non-lipid biomarkers of cardiovascular risk","volume":"13","author":"Faridi","year":"2017","journal-title":"Arch. Med. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e005146","DOI":"10.1161\/CIRCIMAGING.116.005146","article-title":"Effects of liraglutide on reperfusion injury in patients with ST-segment-elevation myocardial infarction","volume":"9","author":"Chen","year":"2016","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00395-020-00829-5","article-title":"Mouse models of atherosclerosis and their suitability for the study of myocardial infarction","volume":"115","author":"Golforoush","year":"2020","journal-title":"Basic Res. Cardiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/4\/920\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:48:52Z","timestamp":1760161732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/4\/920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,16]]},"references-count":57,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cells10040920"],"URL":"https:\/\/doi.org\/10.3390\/cells10040920","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,16]]}}}