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Ample evidence has shown that FA uptake is mediated by plasma membrane transporters including FA transport proteins (FATPs), caveolin-1, fatty-acid translocase (FAT)\/CD36, and fatty-acid binding proteins. Unlike other FA transporters, the functions of FATPs have been controversial because they contain both motifs of FA transport and fatty acyl-CoA synthetase (ACS). The widely distributed FATP4 is not a direct FA transporter but plays a predominant function as an ACS. FATP4 deficiency causes ichthyosis premature syndrome in mice and humans associated with suppression of polar lipids but an increase in neutral lipids including triglycerides (TGs). Such a shift has been extensively characterized in enterocyte-, hepatocyte-, and adipocyte-specific Fatp4-deficient mice. The mutants under obese and non-obese fatty livers induced by different diets persistently show an increase in blood non-esterified free fatty acids and glycerol indicating the lipolysis of TGs. This review also focuses on FATP4 role on regulatory networks and factors that modulate FATP4 expression in metabolic tissues including intestine, liver, muscle, and adipose tissues. Metabolic disorders especially regarding blood lipids by FATP4 deficiency in different cell types are herein discussed. Our results may be applicable to not only patients with FATP4 mutations but also represent a model of dysregulated lipid homeostasis, thus providing mechanistic insights into obesity and development of fatty liver disease.<\/jats:p>","DOI":"10.1042\/bsr20211854","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T11:35:31Z","timestamp":1652873731000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Role of fatty acid transport protein 4 in metabolic tissues: insights into obesity and fatty liver disease"],"prefix":"10.1042","volume":"42","author":[{"given":"Huili","family":"Li","sequence":"first","affiliation":[{"name":"1Department of Internal Medicine IV, University of Heidelberg Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"},{"name":"2Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Herrmann","sequence":"additional","affiliation":[{"name":"3Westkuesten Hospital, Esmarchstra\u00dfe 50, 25746 Heide, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"See\u00dfle","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University of Heidelberg Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Liebisch","sequence":"additional","affiliation":[{"name":"4Institute of Clinical Chemistry and Laboratory Medicine, University Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Merle","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University of Heidelberg Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Stremmel","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University of Heidelberg Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-7664","authenticated-orcid":false,"given":"Walee","family":"Chamulitrat","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University of Heidelberg Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"2022060618025819300_B1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41574-019-0256-9","article-title":"The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state","volume":"15","author":"Hodson","year":"2019","journal-title":"Nat. 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