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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,6,11]]},"abstract":"<jats:p>\n                    Alcohol dehydrogenase 1B (ADH1B) is a primate-specific enzyme which, uniquely among the ADH class 1 family, is highly expressed both in adipose tissue and liver. Its expression in adipose tissue is reduced in obesity and increased by insulin stimulation. Interference with\n                    <jats:italic>ADH1B<\/jats:italic>\n                    expression has also been reported to impair adipocyte function. To better understand the role of ADH1B in adipocytes, we used CRISPR\/Cas9 to delete\n                    <jats:italic>ADH1B<\/jats:italic>\n                    in human adipose stem cells (ASC). Cells lacking ADH1B failed to differentiate into mature adipocytes manifested by minimal triglyceride accumulation and a marked reduction in expression of established adipocyte markers. As ADH1B is capable of converting retinol to retinoic acid (RA), we conducted rescue experiments. Incubation of ADH1B-deficient preadipocytes with 9-cis-RA, but not with all-transretinol, significantly rescued their ability to accumulate lipids and express markers of adipocyte differentiation. A homozygous missense variant in\n                    <jats:italic>ADH1B<\/jats:italic>\n                    (p.Arg313Cys) was found in a patient with congenital lipodystrophy of unknown cause. This variant significantly impaired the protein\u2019s dimerization, enzymatic activity, and its ability to rescue differentiation in ADH1B-deficient ASC. The allele frequency of this variant in the Middle Eastern population suggests that it is unlikely to be a fully penetrant cause of severe lipodystrophy. In conclusion, ADH1B appears to play an unexpected, crucial and cell-autonomous role in human adipocyte differentiation by serving as a necessary source of endogenous retinoic acid.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2319301121","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T13:39:42Z","timestamp":1717594782000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["ADH1B, the adipocyte-enriched alcohol dehydrogenase, plays an essential, cell-autonomous role in human adipogenesis"],"prefix":"10.1073","volume":"121","author":[{"given":"J\u00e9r\u00e9mie","family":"Gautheron","sequence":"first","affiliation":[{"name":"Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9-Inserm, Paris 75012, France"},{"name":"Foundation for Innovation in Cardiometabolism and Nutrition, Paris 75013, 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