{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:41:23Z","timestamp":1792384883322,"version":"4.4.0"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Animal models of prediabetes (Pre\u2010DM) are essential for studying metabolic disease and testing therapies, yet high\u2010fat diet (HFD) and HFD\u2010plus\u2010streptozotocin (STZ) protocols vary in feeding duration, STZ dose, and diagnostic criteria and rarely account for sex. We compared five protocols in male and female C57BL\/6J mice to find the best balance of duration, cost, and phenotypic stability and to characterize how HFD and HFD\u2010STZ differ in their effects on glucose and lipid metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Five\u2010week\u2010old mice were stratified by sex and assigned to three HFD\u2010only groups (HFD\u201012w, \u201016w, \u201020w) and two STZ groups of differing cumulative dose (HFD\u2010STZ\u2010L, \u2010H). Body weight, food and energy intake, body fat percentage, fasting blood glucose (FBG), OGTT, ITT, fasting insulin, serum lipids, hepatic Oil Red O, histopathology, liver and kidney safety, and per\u2010animal cost were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HFD induced obesity of equal magnitude in both sexes (non\u2010significant Sex \u00d7 Diet interactions for body weight and fat mass). Glucose and hepatic\u2010lipid metabolism showed clear sex dimorphism: in males these deteriorated by Week 12, whereas females required 16\u2009weeks to reach the Pre\u2010DM threshold, at a higher preset STZ dose. HFD\u2010STZ\u2010L matched HFD\u201012w in both sexes within a shorter cycle (overall success 73.3%). Notably, STZ reversed the HFD lipid phenotype, synchronously reducing body fat, serum lipids, and hepatic fat in females.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HFD\u2010STZ\u2010L is preferred for glucose and \u03b2\u2010cell studies in both sexes; HFD\u201012w preserves the intact female obesity phenotype; HFD\u201020w is preferred for MASLD studies. Biological sex must be incorporated into model design and phenotype interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71183","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:39:00Z","timestamp":1786343940000},"page":"9897-9918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic Comparison of High\u2010Fat Diet\u2013 and Streptozotocin\u2010Induced Prediabetic Obese\n                    <scp>C57BL<\/scp>\n                    \/\n                    <scp>6J<\/scp>\n                    Mouse Models: A Sex\u2010Based Protocol Optimization Study"],"prefix":"10.1111","volume":"28","author":[{"given":"Min","family":"Xu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan 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