A novel combined glucocorticoid-mineralocorticoid receptor selective modulator markedly prevents weight gain and fat mass expansion in mice fed a high-fat diet

International Journal of Obesity : Journal of the International Association for the Study of Obesity
Caterina MammiMassimiliano Caprio

Abstract

We have previously shown that antagonism of the mineralocorticoid receptor (MR) results in a potent antiadipogenic activity, in vitro and in vivo. Excessive glucocorticoid exposure is associated with obesity and related disorders in humans and mice. In this study, responses to a novel combined glucocorticoid receptor (GR)/MR antagonist were investigated in a model of diet-induced obesity. Female 10-week-old C57BL/6J mice were fed with normal chow or a high-fat diet (HFD) for 9 weeks. Mice fed a HFD were concomitantly treated for 9 weeks with the GR antagonist mifepristone (80 mg kg(-1) per day) or the novel combined GR/MR antagonist CORT118335 (80 mg kg(-1) per day). Male, juvenile 6-week-old C57BL/6J mice fed HFD were treated with CORT118335 for 4 weeks. Mice fed a HFD showed a significant increase in total body weight and white fat mass, with impaired glucose tolerance and increased fat infiltration in livers. Interestingly, only CORT118335 completely prevented the HFD-induced weight gain and white fat deposition, whereas mifepristone showed no effect on body weight and modestly increased subcutaneous fat mass. Importantly, food intake was not affected by either treatment, and CORT118335 dramatically increased PGC-1α protein ...Continue Reading

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Citations

May 26, 2016·Toxicology Letters·R G Ahmed
Jul 5, 2016·International Journal of Molecular Sciences·Francisco Javier Ruiz-OjedaConcepción María Aguilera
Oct 11, 2016·Mediators of Inflammation·José de Jesús Guerrero-GarcíaDaniel Ortuño-Sahagún
May 23, 2017·American Journal of Respiratory Cell and Molecular Biology·Stephen E McGowan, Diann M McCoy
May 22, 2019·American Journal of Physiology. Endocrinology and Metabolism·Elizabeth T NguyenMatia B Solomon
Apr 5, 2020·International Journal of Molecular Sciences·Alejandro F De NicolaMaria Claudia Gonzalez Deniselle
Apr 22, 2017·Molecular Cancer Therapeutics·Jacob KachRussell Z Szmulewitz
Feb 3, 2021·Journal of Human Hypertension·Moe Thuzar, Michael Stowasser
Aug 27, 2018·The Journal of Steroid Biochemistry and Molecular Biology·Thi Thu Huong DoBuyse Marion

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