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We previously reported that Pex14, a peroxin protein involved in the biogenesis and degradation of peroxisomes, is markedly reduced in the pancreas of an intrauterine growth restriction fetus and last into adulthood. Peroxisomes function in a wide range of metabolic processes including fatty acid oxidization, ROS detoxification, and anti\u2010inflammatory responses. To elucidate the impact of downregulation of the Pex14 gene on <jats:italic>\u03b2<\/jats:italic> cell, Pex14 was knocked down by siRNA in INS\u20101 cells. Pex14 knockdown disturbed peroxisomal biogenesis and dysregulated fatty acid metabolism and lipid storage capability, thereby increased ROS level and blunted insulin secretion. Moreover, Pex14 knockdown upregulated inflammation factors and regulators of endoplasmic reticulum stress. The lipotoxicity of fatty acid (including palmitic acid and linoleic acid) in <jats:italic>\u03b2<\/jats:italic> cells was exacerbated by knockdown of Pex14, as indicated by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> accumulation and increased programmed cell death. The present results demonstrate the vital role of Pex14 in maintaining normal peroxisome function and <jats:italic>\u03b2<\/jats:italic> cell viability and highlight the importance of a functional peroxisomal metabolism for the detoxification of excess FAs in <jats:italic>\u03b2<\/jats:italic> cells.<\/jats:p>","DOI":"10.1155\/2021\/7726058","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T01:05:09Z","timestamp":1629767109000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Peroxisome Deficiency Dysregulates Fatty Acid Oxidization and Exacerbates Lipotoxicity in <i>\u03b2<\/i> 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