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.