Mifepristone promotes adiponectin production and improves insulin sensitivity in a mouse model of diet-induced-obesity.
The steroid receptor antagonist mifepristone is used as an anti-cancer agent, eliciting both cytostatic and cytotoxic effects on malignant cells. However, the metabolic effects of long-term treatment with mifepristone have remained unclear. The effects of mifepristone on insulin sensitivity and adiponectin secretion were evaluated both in in vivo and in vitro. First, we explored the effects of mifepristone, on metabolic functions in obese mice receiving a high-fat diet. When these mice were fed mifepristone, they exhibited a marked improvement in insulin sensitivity, attenuated hepatic injury, and decreased adipocyte size, compared with mice that received only the high-fat diet. Intriguingly, mifepristone-treated mice showed significantly elevated plasma adiponectin levels. Second, we tested the effects of mifepristone on differentiated 3T3-L1 adipocytes in vitro. When differentiated adipocytes were treated with mifepristone for 48 h, adiponectin was upregulated at both mRNA and protein levels. Collectively, these results reveal novel actions of mifepristone on metabolic functions, in vivo and in vitro, in which the drug exerts antidiabetic effects associated with an upregulation in adiponectin-secretion.
Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Takeshi
T
Hashimoto
Junsuke
J
Igarashi
Arif U
AU
Hasan
Koji
K
Ohmori
Masakazu
M
Kohno
Yukiko
Y
Nagai
Tetsuo
T
Yamashita
Hiroaki
H
Kosaka
D041721:3T3-L1 Cells; D052242:Adiponectin / Q000096:biosynthesis*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology* / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D052242:Adiponectin; D015735:Mifepristone