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Considering tumor is a type of metabolic disease, we investigated the metabolomics changes in serum and tumor after apatinib treatment and the molecular mechanism of characteristic changes associated with its antitumor efficacy. Molecules in serum and tumor tissue were extracted and analyzed by a gas chromatography\u2010mass spectrometry metabolic platform. Apatinib significantly inhibited e tumor growth and alleviated metabolic rearrangement in both serum and tumor of A549 xenograft mice. Among these endogenous metabolites, 3\u2010hydroxybutyric acid (3\u2010<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>) was significantly increased in serum, tumor and liver after apatinib treatment. Interestingly, giving exogenous 3\u2010<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> also inhibited tumor growth. Gene expression, dual luciferase reporter gene assay and molecular docking analysis all indicated that apatinib could induce 3\u2010<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> production through the dependent activation of peroxisome proliferator\u2010activated receptor \u03b1 (<jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1) and promotion of fatty acid utilization in the liver. Therefore, increased content of 3\u2010<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> induced by <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 activation in the liver partially contributed to the antitumor effect of apatinib. It may provide clues to another potential mechanism underlying the antitumor effect of apatinib besides its antiangiogenic effect through inhibiting vascular endothelial growth factor receptor 2.<\/jats:p>","DOI":"10.1111\/cas.14168","type":"journal-article","created":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T04:58:40Z","timestamp":1566277120000},"page":"3328-3339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Apatinib induces 3\u2010hydroxybutyric acid production in the liver of mice by peroxisome proliferator\u2010activated receptor \u03b1 activation to aid its antitumor effect"],"prefix":"10.1111","volume":"110","author":[{"given":"Siqi","family":"Feng","sequence":"first","affiliation":[{"name":"Key Laboratory of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing China"},{"name":"School of Pharmaceutical Sciences Zhengzhou 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