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Dietary Fat Composition Modifies Cell Sphingolipid Biosynthesis to Mediate the consequences of obesity.
Author(s) -
Cowart L. Ashley
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.453.2
Subject(s) - sphingolipid , ceramide , fatty liver , obesity , type 2 diabetes , endocrinology , lipid metabolism , biology , medicine , disease , diabetes mellitus , autophagy , microbiology and biotechnology , biochemistry , apoptosis
Obesity is associated with type 2 diabetes, non‐alcoholic fatty liver disease, and cardiovascular disease, but mechanisms by which obesity may promote these disease states are not fully understood. We demonstrate that in obesity, dietary fat composition is reflected in plasma lipid profiles, and differential lipid supply to cells profoundly impacts the biosynthesis of bioactive sphingolipids including ceramides and sphingosine‐1‐phosphate, which mouse obesity models indicate mediate obesity‐induced disease. We have used these models as well as cultured cells to identify specific pathways of sphingolipid metabolism that underlie obesity‐induced diseases including non‐alcoholic fatty liver disease and diabetic cardiomyopathy. Specifically, data demonstrated that Ceramide Synthase 5 regulated cardiac myocyte autophagy and subsequent hypertrophy, and our data also suggest roles for sphingosine kinase 1 in mediating inflammatory processes associated with obesity. We propose that these pathways constitute novel therapeutic targets for obesity‐associated disease.