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Patatin‐like phospholipase domain‐containing protein 3 is involved in hepatic fatty acid and triglyceride metabolism through X‐box binding protein 1 and modulation of endoplasmic reticulum stress in mice
Author(s) -
Ochi Tsunehiro,
Munekage Kensuke,
Ono Masafumi,
Higuchi Takuma,
Tsuda Masayuki,
Hayashi Yoshihiro,
Okamoto Nobuto,
Toda Katsumi,
Sakamoto Shuji,
Oben Jude A.,
Saibara Toshiji
Publication year - 2016
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12587
Subject(s) - endoplasmic reticulum , triglyceride , phospholipase , chemistry , fatty acid , fatty acid binding protein , lipid metabolism , biochemistry , microsomal triglyceride transfer protein , fatty acid metabolism , metabolism , enzyme , gene , cholesterol , lipoprotein , very low density lipoprotein
Aim Non‐alcoholic steatohepatitis (NASH) is the major cause of chronic liver disease worldwide. Endoplasmic reticulum (ER) stress is considered to be an important pathological characteristic in NASH. A sequence variation (I148M) in the patatin‐like phospholipase domain‐containing protein 3/adiponutrin (PNPLA3) gene is known to be associated with the development of NASH. However, PNPLA3 deficiency has been considered to not be associated with fatty liver disease. To clarify, therefore, the role of PNPLA3 in liver, we established PNPLA3 knockout (KO) mice and investigated the phenotypes and involved factors under ER stress. Methods ER stress was induced by i.p. injection with tunicamycin or with saline at 0 and 24 h in KO and C57BL/6 (wild‐type [WT]) mice. At 48 h after the starting of treatment, blood and liver samples were studied. Results Hepatic steatosis and triglyceride content were remarkably increased in WT mice than in KO mice under ER stress. The hepatic palmitate/oleate ratio was significantly higher originally in KO mice than in WT mice. Moreover, the expression of stearoyl‐coenzyme A desaturase‐1 (SCD1) in KO mice under ER stress was decreased further than that in WT mice. Expression of ER stress markers X‐box binding protein 1 (XBP1) and ERdj4 was increased in WT mice but not in KO mice under ER stress. Conclusion We first demonstrated the hepatic phenotype of PNPLA3 deficiency under ER stress. Our observations would indicate that PNPLA3 has an important role in hepatic fatty acid metabolism and triglyceride accumulation through XBP1 under ER stress.