Publication

Free fatty acids sensitize hepatocytes to bile acid-induced apoptosis

Journal Paper/Review - Apr 29, 2008

Units
PubMed
Doi

Citation
Pusl T, Wild N, Vennegeerts T, Wimmer R, Göke B, Brand S, Rust C. Free fatty acids sensitize hepatocytes to bile acid-induced apoptosis. Biochem Biophys Res Commun 2008; 371:441-5.
Type
Journal Paper/Review (English)
Journal
Biochem Biophys Res Commun 2008; 371
Publication Date
Apr 29, 2008
Issn Electronic
1090-2104
Pages
441-5
Brief description/objective

Delivery of free fatty acids to the liver in nonalcoholic fatty liver disease (NAFLD) may render hepatocytes more vulnerable to glycochenodeoxycholic acid (GCDCA)-induced apoptosis. Fat overloading was induced in HepG2-Ntcp cells and primary rat hepatocytes by incubation with palmitic or oleic acid. Apoptosis was quantified by measuring caspase 3/7 activity and transcription of interleukin (IL) 8 and IL-22 by quantitative real-time PCR. Oleic acid (500 microM) alone did not induce apoptosis, while palmitic acid (500 microM) increased apoptosis 5-fold. GCDCA did not induce significant apoptosis at low micromolar concentrations (5-30 microM) in non-steatotic cells. However, at the same concentrations, GCDCA increased apoptosis 3-fold in oleic acid-pretreated HepG2-Ntcp cells and 3.5-fold in primary rat hepatocytes. Pretreatment with oleic acid increased GCDCA-induced gene transcription of the proinflammatory cytokines IL-8 and IL-22 5-fold and 19-fold, respectively. Thus, low levels of cholestasis normally not considered harmful could advance liver injury in patients with NAFLD.