{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:19:26Z","timestamp":1791411566455,"version":"4.3.3"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>In this study, control C57BL\/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary adipocytes differentiated from mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions, such as insulin resistance.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.308749","type":"journal-article","created":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T02:10:32Z","timestamp":1483063832000},"page":"466-475","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":109,"title":["Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity"],"prefix":"10.1161","volume":"37","author":[{"given":"Laura J.","family":"Den Hartigh","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Diabetes and Obesity Center of Excellence (L.J.D.H., M.O., L.G., S.W., C.Y.H.) and Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Omer","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Diabetes and Obesity Center of Excellence (L.J.D.H., M.O., L.G., S.W., C.Y.H.) and Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leela","family":"Goodspeed","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Diabetes and Obesity Center of Excellence (L.J.D.H., M.O., L.G., S.W., C.Y.H.) and Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Diabetes and Obesity Center of Excellence (L.J.D.H., M.O., L.G., S.W., C.Y.H.) and Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Wietecha","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Diabetes and Obesity Center of Excellence (L.J.D.H., M.O., L.G., S.W., C.Y.H.) and Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Diabetes and Obesity Center of Excellence (L.J.D.H., M.O., L.G., S.W., C.Y.H.) and Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Yeop","family":"Han","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Diabetes and Obesity Center of Excellence (L.J.D.H., M.O., L.G., S.W., C.Y.H.) and Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20514"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19451"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19246"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24335"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0218"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0925"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2010.1"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1964"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.165100"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04634"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2001-0039"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21625"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.304998"},{"key":"e_1_3_5_15_2","first-page":"193","article-title":"Anti-obesity effect of two different levels of dehydroepiandrosterone in lean and obese middle-aged female Zucker rats.","volume":"10","author":"Cleary MP","year":"1986","unstructured":"Cleary MP, Zisk JF. 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