Evidence for AMPK-dependent regulation of exocytosis of lipoproteins in a model liver cell line

Livia Puljak, Vinay Parameswara, Svjetlana Dolovcak, Shar L. Waldrop, Daniel Emmett, Victoria Esser, J. Gregory Fitz, Gordan Kilic

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

5′-AMP-activated kinase (AMPK) plays a key role in the regulation of cellular lipid metabolism. The contribution of vesicular exocytosis to this regulation is not known. Accordingly, we studied the effects of AMPK on exocytosis and intracellular lipid content in a model liver cell line. Activation of AMPK by metformin or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) increased the rates of constitutive exocytosis by about 2-fold. Stimulation of exocytosis by AMPK occurred within minutes, and persisted after overnight exposure to metformin or AICAR. Activation of AMPK also increased the amount of triacylglycerol (TG) and apolipoprotein B (apoB) secreted from lipid-loaded cells. These effects were accompanied by a decrease in the intracellular lipid content indicating that exocytosis of lipoproteins was involved in these lipid-lowering effects. While AMPK increased the rates of fatty acid oxidation (FAO), the lipid-lowering effects were quantitatively significant even after inhibition of FAO with R-etomoxir. These results suggest that hepatic AMPK stimulates constitutive exocytosis of lipoproteins, which may function in parallel with FAO to regulate intracellular lipid content.

Original languageEnglish (US)
Pages (from-to)2100-2109
Number of pages10
JournalExperimental Cell Research
Volume314
Issue number10
DOIs
StatePublished - Jun 10 2008

Keywords

  • AMPK
  • Constitutive exocytosis
  • FM1-43
  • Intracellular lipids
  • Nile red

ASJC Scopus subject areas

  • Cell Biology

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