Regulation of adiponectin receptor expression in human liver and a hepatocyte cell line.
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.
Shimizu
Akiko
A
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
Takamura
Toshinari
T
Matsuzawa
Naoto
N
Nakamura
Seiji
S
Nabemoto
Satoko
S
Takeshita
Yumie
Y
Misu
Hirofumi
H
Kurita
Seiichiro
S
Sakurai
Masaru
M
Yokoyama
Masayoshi
M
Zen
Yoh
Y
Sasaki
Motoko
M
Nakanuma
Yasuni
Y
Kaneko
Shuichi
S
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
D007328:Insulin; D054419:Receptors, Adiponectin; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077205:Pioglitazone