title: Regulation of adiponectin receptor expression in human liver and a hepatocyte cell line.
abstract: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. An adipocyte-derived hormone, adiponectin, may play a role in the pathophysiology of NAFLD through insulin-sensitizing and antifibrotic effects. We found that hepatic expression of adiponectin receptor AdipoR2, but not AdipoR1, was down-regulated in 14 patients with NAFLD compared with 7 patients with a normal liver (P < .05). To investigate the significance of the adiponectin system in obesity and NAFLD, we examined the regulation of AdipoR2 expression in a nonmalignant human hepatocyte cell line, the THLE-5b cells. Insulin down-regulated the levels of AdipoR2 messenger RNA (mRNA) and protein, whereas an adipocytokine, tumor necrosis factor alpha, up-regulated them. A thiazolidinedione, pioglitazone, up-regulated the expression of AdipoR2 mRNA and protein in THLE-5b cells. The AdipoR2 mRNA level was decreased in fatty THLE-5b cells induced by coincubating with fatty acids. These findings suggest that down-regulation of AdipoR2 in the liver caused by hyperinsulinemia and steatosis may play a role in the development of NAFLD.
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimizu
authors.forename: Toshinari
authors.initials: T
authors.lastname: Takamura
authors.forename: Naoto
authors.initials: N
authors.lastname: Matsuzawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Satoko
authors.initials: S
authors.lastname: Nabemoto
authors.forename: Yumie
authors.initials: Y
authors.lastname: Takeshita
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Misu
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kurita
authors.forename: Masaru
authors.initials: M
authors.lastname: Sakurai
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D000077205:Pioglitazone; D016133:Polymerase Chain Reaction; D054419:Receptors, Adiponectin / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007328:Insulin; D054419:Receptors, Adiponectin; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077205:Pioglitazone