Journal article
Regulation of plasma ceramide levels with fatty acid oversupply: Evidence that the liver detects and secretes de novo synthesised ceramide
MJ Watt, AC Barnett, CR Bruce, S Schenk, JF Horowitz, AJ Hoy
Diabetologia | SPRINGER | Published : 2012
Abstract
Aims/hypothesis: Plasma ceramide concentrations correlate with insulin sensitivity, inflammation and atherosclerotic risk. We hypothesised that plasma ceramide concentrations are increased in the presence of elevated fatty acid levels and are regulated by increased liver serine C-palmitoyltransferase (SPT) activity. Methods: Lean humans and rats underwent an acute lipid infusion and plasma ceramide levels were determined. One group of lipid-infused rats was administered myriocin to inhibit SPT activity. Liver SPT activity was determined in lipid-infused rats, and obese, insulin resistant mice. The time and palmitate dose-dependent synthesis of intracellular and secreted ceramide was determin..
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Awarded by National Institutes of Health
Funding Acknowledgements
These studies were supported in part by research grants from the National Health and Medical Research Council (NHMRC) of Australia and a Monash University Fellowship, and the National Institutes of Health. A.J. Hoy is supported by an NHMRC Biomedical Australian Training Fellowship, C. R. Bruce an NHMRC Career Development Award, and M.J. Watt by a NHMRC Senior Research Fellowship. J.F. Horowitz is supported by grants from the National Institutes of Health (NIH; R01 DK077966 and P30-DK-089503). S. Schenk is supported by grants from the NIH (R24 HD050837, P30 AR058878).