{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:26Z","timestamp":1784557166039,"version":"3.55.0"},"reference-count":48,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Many studies have reported the causes of obese metabolic syndrome (MS); however, the causes of nonobese MS (NMS) remain unknown. In this study, we demonstrated that inflamed dysfunctional adipose tissue plays a crucial role in cholesterol-induced NMS. Control (C), high cholesterol (HC) and HC with 10% fructose in drinking water (HCF) diets were fed to Sprague\u2013Dawley rats for 12 weeks. After 12 weeks, the body weights of the C- and HC-fed rats were comparable, but the weights of the HCF-fed rats were relatively low. Cholesterol caused metabolic problems such as high blood pressure, hypercholesterolemia and hypoinsulinemia. The HCF-fed rats exhibited whole-body insulin resistance with low circulating high-density lipoprotein levels. Increases in the tumor necrosis factor \u03b1 level in the plasma, the number of CD68+ macrophages and the free nuclear factor-\u03baB level in gonadal white adipose tissue (gWAT) resulted in local inflammation, which appeared as inflamed dysfunctional gWAT. Reduced superoxide dismutases (SODs) deteriorate natural antioxidant defense systems and induce reactive oxygen species in gWAT. Dysregulation of plasma levels of catecholamine, adipokines (leptin and adiponectin), hormone-sensitive lipase and perilipin in cholesterol-induced inflamed adipose tissue contributed to increased lipolysis and increased circulating nonesterified fatty acids. Cholesterol activated inflammation, lipolysis and cell death in 3T3-L1 adipocytes. Moreover, Chol-3T3-CM reduced the population of M2-type Raw264.7 macrophages, indicating that the macrophage polarization is mediated by cholesterol. Together, our findings indicate that inflamed dysfunctional adipocytes are critical in NMS, supporting the development of anti-inflammatory agents as potential therapeutic drugs for treating NMS.<\/jats:p>","DOI":"10.1530\/jme-17-0194","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T12:30:29Z","timestamp":1522067429000},"page":"309-323","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":9,"title":["Role of dysfunctional adipocytes in cholesterol-induced nonobese metabolic syndrome"],"prefix":"10.1530","volume":"60","author":[{"given":"Jiung-Pang","family":"Huang","sequence":"first","affiliation":[{"name":"1Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan"},{"name":"2Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Chieh","family":"Hsu","sequence":"additional","affiliation":[{"name":"1Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan"},{"name":"3Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaa-Jyuhn James","family":"Meir","sequence":"additional","affiliation":[{"name":"1Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan"},{"name":"4Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taiwan"},{"name":"5Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Shiuan","family":"Hsieh","sequence":"additional","affiliation":[{"name":"6Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chun","family":"Chang","sequence":"additional","affiliation":[{"name":"7Department of Clinical Pathology, Far Eastern Memorial Hospital, New Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Hsing","family":"Chen","sequence":"additional","affiliation":[{"name":"8Kidney Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Kan","family":"Chen","sequence":"additional","affiliation":[{"name":"2Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan"},{"name":"9Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Man","family":"Hung","sequence":"additional","affiliation":[{"name":"1Department and Graduate Institute of Biomedical 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