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Our hypothesis was that Vitamin D3 (VitD3) inhibits the growth of adipocyte size by suppressing PPAR\u03b3 expression in white adipocytes of obese mice. Five\u2010week\u2010old male C57BL\/6J mice were randomly divided into normal diet and high\u2010fat diet groups. After 10\u2009weeks, the body weight between the two groups differed by 26.91%. The obese mice were randomly divided into a high\u2010fat diet, solvent control, low\u2010dose VitD3 (5000\u2009IU\/kg\u00b7food), medium\u2010dose VitD3 (7500\u2009IU\/kg\u00b7food), high\u2010dose VitD3 (10,000\u2009IU\/kg\u00b7food), and PPAR \u03b3 antagonist group, and the intervention lasted for 8\u2009weeks. Diet\u2010induced obesity (DIO) mice fed high\u2010dose VitD3 exacerbated markers of adiposity (body weight, fat mass, fat mass rate, size of white and brown adipocytes, mRNA, and protein levels of ATGL and Fsp27), and the protein level of ATGL and Fsp27 decreased in the low\u2010dose group. In conclusion, high\u2010dose VitD3 possibly via inhibiting the ATGL expression, thereby inhibiting lipolysis, increasing the volume of adipocytes, and decreasing their fat\u2010storing ability resulted in decreased Fsp27 expression. Therefore, long\u2010term high\u2010dose oral VitD3 may not necessarily improve obesity, and we need more clinical trials to explore the intervention dose and duration of VitD3 in the treatment of VitD3 deficiency in obese patients.<\/jats:p>","DOI":"10.1002\/fsn3.3618","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T04:38:30Z","timestamp":1692938310000},"page":"6686-6697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of vitamin D3 on lipid droplet growth in adipocytes of mice with HFD\u2010induced obesity"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-6729","authenticated-orcid":false,"given":"Jingjing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition Affiliated Hospital of Southwest Medical University  Luzhou Sichuan 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