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Farnesol suppresses lipid accumulation in a HepaRG‐based model of hepatic steatosis (1142.8)
Author(s) -
Pant Asmita,
Kocarek Thomas
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1142.8
Subject(s) - steatosis , farnesol , hepatic stellate cell , chemistry , lipid metabolism , oleic acid , lipid droplet , farnesoid x receptor , constitutive androstane receptor , receptor , hepatocyte , endocrinology , medicine , biochemistry , nuclear receptor , biology , in vitro , gene , transcription factor
Non‐alcoholic fatty liver disease is one the most common metabolic syndromes characterized by accumulation of triglycerides (TG) in liver. Treatment with the endogenous isoprenoid farnesol lowers hepatic TG levels in rodents, and this effect appears to involve at least two nuclear receptors, peroxisome proliferator‐activated receptor α and farnesoid X receptor (FXR). Activation of constitutive androstane receptor (CAR) has also been shown to ameliorate hepatic steatosis in rodents. However, farnesol’s effects on human hepatic lipid metabolism are currently unknown. In this study, we evaluated the effect of farnesol treatment on human hepatic lipid accumulation in a cellular model of hepatic steatosis that was created by incubating the hepatocyte‐like HepaRG cell line with oleic acid. Incubation of differentiated HepaRG cells with oleic acid produced concentration‐ and time‐dependent increases in intracellular lipid droplets labeled with Oil Red O as well as in TG levels. This TG accumulation was suppressed by 32% when the oleate‐loaded HepaRG cells were co‐treated with farnesol. Farnesol treatment also caused concentration‐ and time‐dependent increases in the mRNA levels of small heterodimer partner and CYP2B6 in HepaRG cells, which are the targets of FXR and CAR, respectively. These results suggest that farnesol treatment can decrease fatty acid‐induced hepatic lipid accumulation in HepaRG cells, possibly by activating FXR and/or CAR. Grant Funding Source : Supported by NIH grant HL050710