{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:44:53Z","timestamp":1792244693024,"version":"4.4.0"},"reference-count":44,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":71,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2014M3A9B6069338"],"award-info":[{"award-number":["NRF-2014M3A9B6069338"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2014M3A9D5A01073886"],"award-info":[{"award-number":["NRF-2014M3A9D5A01073886"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:p>Sphingolipids have been implicated in the etiology of chronic metabolic diseases. Here, we investigated whether sphingolipid biosynthesis is associated with the development of adipose tissues and metabolic diseases. SPTLC2, a subunit of serine palmitoyltransferase, was transcriptionally upregulated in the adipose tissues of obese mice and in differentiating adipocytes. Adipocyte-specific SPTLC2-deficient (aSPTLC2 KO) mice had markedly reduced adipose tissue mass. Fatty acids that were destined for the adipose tissue were instead shunted to liver and caused hepatosteatosis. This impaired fat distribution caused systemic insulin resistance and hyperglycemia, indicating severe lipodystrophy. Mechanistically, sphingosine 1-phosphate (S1P) was reduced in the adipose tissues of aSPTLC2 KO mice, and this inhibited adipocyte proliferation and differentiation via the downregulation of S1P receptor 1 and decreased activity of the peroxisome proliferator\u2013activator receptor \u03b3. In addition, downregulation of SREBP (sterol regulatory element\u2013binding protein)-1c prevented adipogenesis of aSPTLC2 KO adipocytes. Collectively, our observations suggest that the tight regulation of de novo sphingolipid biosynthesis and S1P signaling plays an important role in adipogenesis and hepatosteatosis.<\/jats:p>","DOI":"10.2337\/db16-1232","type":"journal-article","created":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T00:25:23Z","timestamp":1499819123000},"page":"2596-2609","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":63,"title":["Adipocyte-Specific Deficiency of De Novo Sphingolipid Biosynthesis Leads to Lipodystrophy and Insulin Resistance"],"prefix":"10.2337","volume":"66","author":[{"given":"Su-Yeon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Life Science, Gachon University, Sungnam, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes 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