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Olivera, A., Kohama, T., Edsall, L., Nava, V., Cuvillier, O., Poulton, S. and Spiegel, S. (1999) Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival. Journal of Cell Biology, 147, 545-558. doi:10.1083/jcb.147.3.545

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• TITLE: Obesity-associated steatotic liver exhibits aberrant or altered sphingolipid composition and preferentially accumulates ceramide species containing long chain fatty acids

  AUTHORS: Erin L. Burrows, Ranjana P. Bird

  KEYWORDS: Sphingolipids; Obesity; Zucker Obese Rats; Apoptosis; Hepatic Steatosis

  JOURNAL NAME: Health, Vol.4 No.12A, December 31, 2012

  ABSTRACT: The sphingolipid (SL) signaling pathways are induced by reactive oxygen species and proin-flammatory molecules, which are shown to be upregulated in the obese state. The present work was conducted to determine if an altered SL pathway exists, and contributes to the pathogenesis of hepatic steatosis associated with obesity. Steatotic and non-steatotic livers were procured from Zucker Obese female rats and their lean counterparts in this pre-clinical study, and assessed for enzymes involved in degradation as well as in phos-phorylation of proapoptotic SLs. The expression of enzymes [sphingo-myelinase (SMase), ceramidase, and sphingosine kinase-1 (SK1)] and apoptotic proteins (Bax and Bcl-2) was quantified by ELISA and by Western Blot. Sphingomyelin (SM), ceramide, ceramide-1 phosphate (C1P), sphingosine (SPH), and sphingosine-1-phosphate (S1P) levels were quantified by high-performance liquid chroma-tography (HPLC)-tandem mass spectroscopy (MS). Obese steatotic livers exhibited significantly upregulated ceramidase and down-regulated SK1 and C1P levels (P accumulation of ceramides containing long chain fatty acids could be involved in the pathogenesis of hepatic steatosis.