Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1949155 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2014 | 13 Pages |
Abstract
Ceramide synthase 2 (CerS2) null mice cannot synthesize very-long acyl chain (C22-C24) ceramides resulting in significant alterations in the acyl chain composition of sphingolipids. We now demonstrate that hepatic triacylglycerol (TG) levels are reduced in the liver but not in the adipose tissue or skeletal muscle of the CerS2 null mouse, both before and after feeding with a high fat diet (HFD), where no weight gain was observed and large hepatic nodules appeared. Uptake of both BODIPY-palmitate and [3H]-palmitate was also abrogated in the hepatocytes and liver. The role of a number of key proteins involved in fatty acid uptake was examined, including FATP5, CD36/FAT, FABPpm and cytoplasmic FABP1. Levels of FATP5 and FABP1 were decreased in the CerS2 null mouse liver, whereas CD36/FAT levels were significantly elevated and CD36/FAT was also mislocalized upon insulin treatment. Moreover, treatment of hepatocytes with C22-C24-ceramides down-regulated CD36/FAT levels. Infection of CerS2 null mice with recombinant adeno-associated virus (rAAV)-CerS2 restored normal TG levels and corrected the mislocalization of CD36/FAT, but had no effect on the intracellular localization or levels of FATP5 or FABP1. Together, these results demonstrate that hepatic fatty acid uptake via CD36/FAT can be regulated by altering the acyl chain composition of sphingolipids.
Keywords
SLSFATPFABPpmCerSDRMSVLCFABPCD36/FATNAFLDplasma membrane fatty acid binding proteinHFDSSOLCFAFFAsphingolipidssphingolipidFree fatty acidlong chain fatty acidfatty acid translocaseNonalcoholic fatty liver diseasetriacylglycerolFatty acid uptakecluster of differentiation 36High fat dietceramide synthaseDetergent resistant membranesFatty acid binding proteinFatty acid transport protein
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Woo-Jae Park, Joo-Won Park, Alfred H. Jr., Judith Storch, Yael Pewzner-Jung, Anthony H. Futerman,