Hepatic fatty acid uptake is regulated by the sphingolipid acyl chain length

Woo Jae Park, Joo Won Park, Alfred H. Merrill, Judith Storch, Yael Pewzner-Jung, Anthony H. Futerman

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1754-1766
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1841
Issue number12
DOIs
StatePublished - Jan 1 2014

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Sphingolipids
Fatty Acids
Liver
Palmitates
Hepatocytes
Triglycerides
Dependovirus
High Fat Diet
Weight Gain
Adipose Tissue
Skeletal Muscle
Insulin
Mouse Cers2 protein
Infection
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • Ceramide synthase
  • Cluster of differentiation 36
  • Fatty acid binding protein
  • Fatty acid transport protein
  • Fatty acid uptake
  • Sphingolipid

Cite this

Park, Woo Jae ; Park, Joo Won ; Merrill, Alfred H. ; Storch, Judith ; Pewzner-Jung, Yael ; Futerman, Anthony H. / Hepatic fatty acid uptake is regulated by the sphingolipid acyl chain length. In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2014 ; Vol. 1841, No. 12. pp. 1754-1766.
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Hepatic fatty acid uptake is regulated by the sphingolipid acyl chain length. / Park, Woo Jae; Park, Joo Won; Merrill, Alfred H.; Storch, Judith; Pewzner-Jung, Yael; Futerman, Anthony H.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1841, No. 12, 01.01.2014, p. 1754-1766.

Research output: Contribution to journalArticle

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AU - Park, Woo Jae

AU - Park, Joo Won

AU - Merrill, Alfred H.

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AU - Futerman, Anthony H.

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KW - Ceramide synthase

KW - Cluster of differentiation 36

KW - Fatty acid binding protein

KW - Fatty acid transport protein

KW - Fatty acid uptake

KW - Sphingolipid

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