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Human preadipocytes were induced to differentiate in insulin, dexamethasone, triiodothyronine, and 3-isobutyl-1-methylxanthine in the presence or absence of inhibitors and the peroxisome proliferator-activated receptor (PPAR)-\u03b3 activator rosiglitazone. Differentiation was assessed by measuring leptin secretion, lipid content, and lipogenic activity. Rosiglitazone increased cell protein by 15%, the lipid content of the cell layer was doubled, and the lipogenic activity increased sevenfold but did not stimulate leptin secretion. None of the inhibitors significantly inhibited protein content over 20 days, but lipid content and lipogenic activity were inhibited by p70S6 kinase and p38 MAPK inhibition but not by p42\/44 MAPK or PI3K inhibition. All of the inhibitors significantly decreased leptin secretion, and these inhibitory effects were increased by coincubation with rosiglitazone. We conclude that PI3K and p42\/44 MAPK pathways are not critical to the differentiation program leading to lipid accumulation, but stimulation of leptin secretion is dependent on these as well as the p70S6 kinase and p38 MAPK signaling pathways.<\/jats:p>","DOI":"10.2337\/diabetes.52.1.43","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"43-50","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":42,"title":["Differential Regulation of Lipogenesis and Leptin Production by Independent Signaling Pathways and Rosiglitazone During Human Adipocyte Differentiation"],"prefix":"10.2337","volume":"52","author":[{"given":"Nayan G.","family":"Patel","sequence":"first","affiliation":[{"name":"Division of Medical Sciences, University of Birmingham, Birmingham, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie C.","family":"Holder","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Harlow, Essex, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Smith","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Harlow, Essex, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Birmingham, Birmingham, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret C.","family":"Eggo","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Birmingham, Birmingham, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208000927200_R1","doi-asserted-by":"crossref","unstructured":"Pi-Sunyer FX: The medical risks of obesity. 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