title: Adiponectin suppresses endoplasmic reticulum stress in nonalcoholic steatohepatitis.
abstract: In this study, we examined whether adiponectin suppresses endoplasmic reticulum (ER) stress in nonalcoholic steatohepatitis (NASH) using male transgenic mice expressing nSREBP-1c in adipose tissue, nSREBP-1c/adiponectin double-transgenic mice expressing human adiponectin in the liver, and wild-type male mice as the control. Histological findings similar to those observed in liver specimens from patients with NASH were observed in the livers from the nSREBP-1c transgenic mice at 30 weeks of age. By contrast, the NASH-like liver histology was markedly attenuated in age-matched nSREBP-1c/adiponectin double-transgenic mice. The nSREBP-1c/adiponectin double-transgenic mice showed human adiponectin production in the liver and a restored circulating human adiponectin level. Human adiponectin messenger ribonucleic acid (mRNA) expression in the liver was identified in the nSREBP-1c/adiponectin double-transgenic mice, but adiponectin receptor 1 and 2 mRNA expression in the liver was normal. TNFα mRNA was decreased in the liver of the nSREBP-1c/adiponectin double-transgenic mice compared with the nSREBP-1c transgenic mice. The protein expressions of X-box-binding protein-1, activating transcription factor 4, acetyl-CoA carboxylase, TNFα and NFκB were down-regulated in liver tissues from the nSREBP-1c/adiponectin double-transgenic mice. Mouse adiponectin and activating transcription factor 6 expressions were almost the same in the three groups. Post-load plasma glucose levels were significantly lower in the nSREBP-1c/adiponectin double-transgenic mice compared with the nSREBP-1c transgenic mice. These results indicate that adiponectin expressed in the liver suppresses ER stress and attenuates hepatic steatosis, inflammation and insulin resistance in NASH. Adiponectin may open the way to novel therapies for human NASH.
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University;
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.forename: Anna
authors.initials: A
authors.lastname: Nakamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Otabe
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yuan
authors.forename: Tomoka
authors.initials: T
authors.lastname: Fukutani
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada