Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis

Shaikh Mizanoor Rahman, Ishtiaq Qadri, Rachel C. Janssen, Jacob E. Friedman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Adiponectin receptors play a key role in steatosis and inflammation; however, very little is known about regulation of adiponectin receptors in liver. Here, we examined the effects of palmitate loading, endoplasmic reticulum (ER) stress, and the hypolipidemic agent fenofibrate on adiponectin receptor R2 (AdipoR2) levels and AMP-activated protein kinase (AMPK) in human hepatoma Huh7 cells and in Huh.8 cells, a model of hepatitis C-induced steatosis. Palmitate treatment reduced AdipoR2 protein and basal AMPK phosphorylation in Huh7 cells. Fenofibrate treatment preserved AdipoR2 and phosphorylated AMPK (pAMPK) levels in palmitate-treated cells accompanied by reduced triglyceride (TG) accumulation and less activation of ER stress markers CCAAT/enhancer binding (C/EBPβ) and eukaryotic translation initiation factor 2. ER stress agents thapsigargin and tunicamycin suppressed AdipoR2 and pAMPK levels in Huh7 cells, while fenofibrate and the chemical chaperone 4-phenylbutyrate (PBA) prevented these changes. AdipoR2 levels were lower in Huh.8 cells and fenofi brate treatment increased AdipoR2 while reducing activation of c-Jun N-terminal kinase and C/EBP b expression without changing TG levels. Taken together, these results suggest that fatty acids and ER stress reduce AdipoR2 protein and pAMPK levels, while fenofi brate and PBA might be important therapeutic agents to correct lipid- and ER stress-mediated loss of AdipoR2 and pAMPK associated with non-alcoholic steatohepatitis.

Original languageEnglish
Pages (from-to)2193-2202
Number of pages10
JournalJournal of lipid research
Volume50
Issue number11
DOIs
StatePublished - 2009

Keywords

  • Diabetes
  • Inflammation
  • Insulin resistance
  • Obesity
  • Palmitate
  • Signal transduction

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