New role of irisin in hepatocytes: The protective effect of hepatic steatosis in vitro.
Irisin is a newly identified myokine related to exercise and the browning of white fat. Recently, it was reported that irisin serum levels are associated with intrahepatic triglyceride content, suggesting that it might have an important role in the liver. The aim of this study was to determine the role of irisin in hepatocytes. Specifically, the effect of recombinant irisin on palmitic acid (PA)-induced lipogenesis and its related signal pathways were examined in AML12 cells and mouse primary hepatocytes. In the present study, we observed the presence of irisin inside the cells in response to the treatment of recombinant irisin by flow cytometry and cell imaging technique. Recombinant irisin significantly inhibited the PA-induced increase in lipogenic markers ACC and FAS at the mRNA and protein levels, and prevented the PA-induced lipid accumulation in hepatocytes. Additionally, irisin inhibited the PA-induced increase in the expression, nuclear localization, and transcriptional activities of the master regulators of lipogenesis (LXRα and SREBP-1c). Moreover, irisin attenuated PA-induced oxidative stress, which was confirmed by measuring the expression of inflammatory markers (NFκB, COX-2, p38 MAPK, TNF, IL-6) and superoxide indicator (dihydroethidium). The preventive effects of irisin against lipogenesis and oxidative stress were mediated by the inhibition of protein arginine methyltransferase-3 (PRMT3). These findings suggested that irisin might have a beneficial role in the prevention of hepatic steatosis by altering the expression of lipogenic genes and attenuating oxidative stress in a PRMT3 dependent manner.
Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Min-Jung
MJ
Park
Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Dong-Il
DI
Kim
Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Joo-Hee
JH
Choi
Department of Food and Nutrition, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: yrhuh@jnu.ac.kr.
Young-Ran
YR
Heo
Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: parksh@chonnam.ac.kr.
Soo-Hyun
SH
Park
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019308:Palmitic Acid / Q000633:toxicity; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D019308:Palmitic Acid
Hepatic lipogenesis PRMT3; Hepatocytes; Irisin