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Previously, we and others have highlighted white adipose tissue (WAT) browning as the main underlying mechanism of IF-mediated metabolic benefits. However, whether IF retains its efficacy in different models, such as genetically obese\/diabetic animals, is unknown. Here, leptin-deficient <jats:italic>ob\/ob<\/jats:italic> mice were subjected to 16 weeks of isocaloric IF, and comprehensive metabolic phenotyping was conducted to assess the metabolic effects of IF. Unlike our previous study, isocaloric IF-subjected <jats:italic>ob\/ob<\/jats:italic> animals failed to exhibit reduced body weight gain, lower fat mass, or decreased liver lipid accumulation. Moreover, isocaloric IF did not result in increased thermogenesis nor induce WAT browning in <jats:italic>ob\/ob<\/jats:italic> mice. These findings indicate that isocaloric IF may not be an effective approach for regulating body weight in <jats:italic>ob\/ob<\/jats:italic> animals, posing the possible limitations of IF to treat obesity. However, despite the lack of improvement in insulin sensitivity, isocaloric IF-subjected <jats:italic>ob\/ob<\/jats:italic> animals displayed improved glucose tolerance as well as higher postprandial insulin level, with elevated incretin expression, suggesting that isocaloric IF is effective in improving nutrient-stimulated insulin secretion. Together, this study uncovers the insulinotropic effect of isocaloric IF, independent of adipose thermogenesis, which is potentially complementary for the treatment of type 2 diabetes.<\/jats:p>","DOI":"10.1038\/s41598-019-39380-2","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T11:03:38Z","timestamp":1550747018000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Thermogenesis-independent metabolic benefits conferred by isocaloric intermittent fasting in ob\/ob mice"],"prefix":"10.1038","volume":"9","author":[{"given":"Yun Hye","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0736-8679","authenticated-orcid":false,"given":"Ju Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna Lan-Hing","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eashita","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ri Youn","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Ho","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyerin","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Thakkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe Eun","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Trzaskalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-chung","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Oh","family":"Doh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Mulvihill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Ryong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Han","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon-Ki","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,21]]},"reference":[{"key":"39380_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/35007508","volume":"404","author":"PG Kopelman","year":"2000","unstructured":"Kopelman, P. 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