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Daily administration of two alternative perfluoroalkyl substances, HFPO2 and HFPO4 (1\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> body weight), for 28\u2009days resulted in hepatomegaly and hepatic histopathological injury in mice, particularly in the HFPO4 group. We generated and compared high\u2010throughput RNA\u2010sequencing data from hepatic tissues in control and treatment group mice to clarify the mechanism of HFPO2 and HFPO4 hepatotoxicity. We identified 146 (101 upregulated, 45 downregulated) and 1295 (716 upregulated, 579 downregulated) hepatic transcripts that exhibited statistically significant changes (fold change \u22652 or \u22640.5, false discovery rate\u00a0&lt;\u00a00.05) after HFPO2 and HFPO4 treatment, respectively. Among them, 111 (82 upregulated, 29 downregulated) transcripts were changed in both groups, and lipid metabolism associated genes were dominant. Thus, similar to their popular predecessors, HFPO2 and HFPO4 exposure exerted hepatic effects, including hepatomegaly and injury, and altered lipid metabolism gene levels in the liver, though HFPO4 exerted greater hepatotoxicity than HFPO2. The unregulated use of these emerging perfluoroalkyl alternatives may affect environmental and human health, and their biological effects need further exploration. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3376","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T02:26:47Z","timestamp":1472005607000},"page":"436-444","source":"Crossref","is-referenced-by-count":72,"title":["RNA\u2010sequencing analysis reveals the hepatotoxic mechanism of perfluoroalkyl alternatives, HFPO2 and HFPO4, following exposure in mice"],"prefix":"10.1002","volume":"37","author":[{"given":"Jianshe","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology Chinese Academy of Sciences  Beijing 100101 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology Chinese Academy of Sciences  Beijing 100101 People's Republic of 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