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Melatonin improves insulin resistance and hepatic steatosis through attenuation of ER stress
Author(s) -
Heo Jeein
Publication year - 2017
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.31.1_supplement.lb221
Subject(s) - melatonin , endocrinology , medicine , insulin resistance , steatosis , fatty liver , insulin , chemistry , disease
Non‐alcoholic fatty liver disease (NAFLD) is increasingly recognized as one of the most common liver diseases. However, there is no specific way to treat or prevent it. Melatonin is a key molecule to regulate body rhythms. It also acts as a potent anti‐oxidant, and the melatonin deficiency is associated with various diseases, including diabetes and obesity; however, the action mechanism is not well known. In addition, fetuin‐A is one of the hepatokines and is known to be associated with insulin resistance and type 2 diabetes. However, it is not known whether melatonin can improve hepatic insulin resistance by down‐regulation of fetuin‐A expression. We used HepG2 cells as a model to study whether melatonin can reduce palmitic acid‐induced insulin resistance. In HepG2 cells treated with (300 uM) of palmitic acid, phosphorylated AKT expression was decreased and fetuin‐A expression was increased, but this effect was inhibited by the treatment of 10 uM of melatonin. Moreover, melatonin decreased palmitic acid‐induced ER stress markers, CHOP, Bip, ATF‐6, XBP‐1, ATF‐4, IRE‐1, and PERK. In addition, thapsigargin, an ER stress activator, increased the expression of fetuin‐A, and ER stress markers, and it was inhibited by melatonin treatment. In addition, in the high fat diet (HFD) mice, oral treatment of 100 mg/kg/day melatonin for 10 weeks decreased body weight, epididymal fat mass, and hepatic steatosis. Insulin sensitivity and glucose tolerance was improved and plasma insulin was decreased by melatonin in HFD mice. Fetuin‐A expression in liver and serum of HFD mice was decreased by melatonin treatment. ER stress markers in liver of HFD mice was decreased by melatonin. Therefore, we suggest that melatonin can improve hepatic insulin resistance and hepatic steatosis, and this may be due to the reduction of ER stress and resultant fetuin‐A expression. Support or Funding Information This work was supported by Research Grant (2015R1C1A2A010520) of National Research Foundation of Korea.