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The liver is enriched with polyunsaturated triglycerides (PUFA\u2010TGs) in PNPLA3\u2010I148M carriers. Gene expression data indicate that PNPLA3 is liver\u2010specific in humans, but whether it functions in adipose tissue (AT) is unknown. We investigated whether PNPLA3\u2010I148M modifies AT metabolism in human NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Profiling of the AT lipidome and fasting serum non\u2010esterified fatty acid (NEFA) composition was conducted in 125 volunteers (<jats:italic>PNPLA3<\/jats:italic><jats:sup>148MM\/MI<\/jats:sup>, n\u00a0=\u00a063; <jats:italic>PNPLA3<\/jats:italic><jats:sup>148II<\/jats:sup>, n\u00a0=\u00a062). AT fatty acid composition was determined in 50 volunteers homozygous for the variant (<jats:italic>PNPLA3<\/jats:italic><jats:sup>148MM<\/jats:sup>, n\u00a0=\u00a025) or lacking the variant (<jats:italic>PNPLA3<\/jats:italic><jats:sup>148II<\/jats:sup>, n\u00a0=\u00a025). Whole\u2010body insulin sensitivity of lipolysis was determined using [<jats:sup>2<\/jats:sup>H<jats:sub>5<\/jats:sub>]glycerol, and PNPLA3 mRNA and protein levels were measured in subcutaneous AT and liver biopsies in a subset of the volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PUFA\u2010TGs were significantly increased in AT in carriers versus non\u2010carriers of PNPLA3\u2010I148M. The variant did not alter the rate of lipolysis or the composition of fasting serum NEFAs. <jats:italic>PNPLA3<\/jats:italic> mRNA was 33\u2010fold higher in the liver than in AT (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001). In contrast, PNPLA3 protein levels per tissue protein were three\u2010fold higher in AT than the liver (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001) and nine\u2010fold higher when related to whole\u2010body AT and liver tissue masses (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Contrary to previous assumptions, PNPLA3 is highly abundant in AT. PNPLA3\u2010I148M locally remodels AT TGs to become polyunsaturated as it does in the liver, without affecting lipolysis or composition of serum NEFAs. Changes in AT metabolism do not contribute to NAFLD in PNPLA3\u2010I148M carriers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14507","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T21:05:16Z","timestamp":1589058316000},"page":"2128-2138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The PNPLA3\u2010I148M variant increases polyunsaturated triglycerides in human adipose tissue"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9313-9324","authenticated-orcid":false,"given":"Sami","family":"Qadri","sequence":"first","affiliation":[{"name":"Department of Medicine University of Helsinki and Helsinki University Hospital Helsinki Finland"},{"name":"Minerva Foundation Institute for Medical Research Helsinki 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