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Protective effect of APLN against liver X receptor‐mediated hepatic steatosis through HG11/APLNR in human and mouse hepatocytes
Author(s) -
Huang Jin,
Kang Saeromi,
Park SooJin,
Im DongSoon
Publication year - 2018
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.2018.32.1_supplement.563.13
Subject(s) - ampk , apelin , steatosis , medicine , endocrinology , liver x receptor , fatty liver , biology , lipogenesis , gene silencing , receptor , transcription factor , microbiology and biotechnology , protein kinase a , lipid metabolism , kinase , gene , nuclear receptor , biochemistry , disease
Background Non‐alcoholic fatty liver disease is the most commonly occurring chronic liver disease, and hepatic steatosis is associated with obesity and type II diabetes. APLN is an adipokine that acts on a G protein‐coupled receptor named HG11/APLNR, and has been established to play pivotal roles in various physiological conditions. However, the function of APLN in hepatocytes has not been fully investigated. METHODS In order to assess the functional roles of APLN and APLNR in hepatocytes, we used an in vitro model of liver X receptor (LXR)‐mediated hepatocellular steatosis. RESULTS In Hep3B human hepatoma cells, T0901317 (a specific LXR activator) induced lipid accumulation and this was inhibited by APLN. T0901317 also induced the expression of SREBP‐1c, a key transcription factor for lipogenesis. APLN not only inhibited SREBP‐1c induction at the mRNA and protein levels but also induced lipolytic PPAR alfa expression. Furthermore, these protective effects of APLN were inhibited by APLN‐F13A (a specific APLNR antagonist). Furthermore, silencing of APLNR by siRNA transfection also inhibited the actions of APLN. Specific inhibitors of cellular signaling components showed inhibition of lipid accumulation by APLN was mediated through Gi/o proteins, AMPK, and SREBP‐1c suppression during the early stage and through AMPK, ERKs, and PPAR alfa induction during the late stage. In addition, the protective effect of APLN was confirmed in mouse primary hepatocytes. CONCLUSION The present findings suggest APLN‐APLNR signaling in hepatocytes functions to protect against lipid accumulation in liver through two signaling pathways, that is, via AMPK activation and PPAR alfa induction. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .