Deletion of the nuclear receptor RORα in macrophages does not modify the development of obesity, insulin resistance and NASH

巨噬细胞中核受体 RORα 的删除不会改变肥胖、胰岛素抵抗和 NASH 的发展

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作者:Laurent L'homme, Benan Pelin Sermikli, Olivier Molendi-Coste, Sébastien Fleury, Sandrine Quemener, Mathilde Le Maître, Marie-Laure Joseph, Laurent Pineau, Christian Duhem, Barbara Gross, Emmanuelle Vallez, Anne Tailleux, Bart Staels, David Dombrowicz

Abstract

Retinoic acid receptor-related orphan receptor-alpha (RORα) is a transcription factor from the nuclear receptor family expressed by immune cells and involved in the development of obesity, insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). It was recently reported that mice deficient for RORα in macrophages develop more severe NASH upon high fat diet (HFD) feeding due to altered Kupffer cell function. To better understand the role of RORα in obesity and IR, we independently generated a macrophage RORα-deficient mouse line. We report that RORα deletion in macrophages does not impact on HFD-induced obesity and IR. Surprisingly, we did not confirm an effect on NASH development upon HFD feeding nor in the more severe and obesity-independent choline-deficient, L-amino acid-defined diet model. Our results therefore show that RORα deletion in macrophages does not alter the development of obesity and IR and question its role in NASH.

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