{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:45:08Z","timestamp":1792244708496,"version":"4.4.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:p>\n                    Adipose dysfunction resulting from chronic inflammation and impaired adipogenesis has increasingly been recognized as a major contributor to obesity-mediated insulin resistance, but the molecular mechanisms that maintain healthy adipocytes and limit adipose inflammation remain unclear. Here, we used genetic and pharmacological approaches to delineate a novel role for sphingosine kinase 1 (SK1) in metabolic disorders associated with obesity. SK1 phosphorylates sphingosine to form sphingosine 1 phosphate (S1P), a bioactive sphingolipid with numerous roles in inflammation. SK1 mRNA expression was increased in adipose tissue of diet-induced obese (DIO) mice and obese type 2 diabetic humans. In DIO mice, SK1 deficiency increased markers of adipogenesis and adipose gene expression of the anti-inflammatory molecules IL-10 and adiponectin and reduced adipose tissue macrophage (ATM) recruitment and proinflammatory molecules TNF\u03b1 and IL-6. These changes were associated with enhanced insulin signaling in adipose and muscle and improved systemic insulin sensitivity and glucose tolerance in SK1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Specific pharmacological inhibition of SK1 in WT DIO mice also reduced adipocyte and ATM inflammation and improved overall glucose homeostasis. These data suggest that the SK1-S1P axis could be an attractive target for the development of treatments to ameliorate adipose inflammation and insulin resistance associated with obesity and type 2 diabetes.\n                  <\/jats:p>","DOI":"10.1152\/ajpendo.00549.2013","type":"journal-article","created":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T21:39:16Z","timestamp":1390945156000},"page":"E756-E768","source":"Crossref","is-referenced-by-count":98,"title":["Sphingosine kinase 1 regulates adipose proinflammatory responses and insulin resistance"],"prefix":"10.1152","volume":"306","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Torrey Pines Institute for Molecular Studies, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leylla","family":"Badeanlou","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Torrey Pines Institute for Molecular Studies, 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