Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma

Abstract Obesity is a well-known risk factor for the development of secondary complications such as type 2 diabetes. However, only a part of the obese population develops secondary metabolic disorders. Here, we identify the transcription factor retinoid-related orphan receptor gamma (ROR?) as a nega...

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Autores principales: Meissburger, Bettina (Autor) , Ukropec, Jozef (Autor) , Roeder, Eva (Autor) , Beaton, Nigel (Autor) , Geiger, Matthias (Autor) , Teupser, Daniel (Autor) , Civan, Burcak (Autor) , Langhans, Wolfgang (Autor) , Nawroth, Peter Paul (Autor) , Gasperikova, Daniela (Autor) , Rudofsky, Gottfried (Autor) , Wolfrum, Christian (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: 19 August 2011
In: EMBO molecular medicine
Year: 2011, Volumen: 3, Número: 11, Pages: 637-651
ISSN:1757-4684
DOI:10.1002/emmm.201100172
Acceso en línea:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/emmm.201100172
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.1002/emmm.201100172
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Notas de Autor:Bettina Meissburger, Jozef Ukropec, Eva Roeder, Nigel Beaton, Matthias Geiger, Daniel Teupser, Burcak Civan, Wolfgang Langhans, Peter P. Nawroth, Daniela Gasperikova, Gottfried Rudofsky, Christian Wolfrum
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Sumario:Abstract Obesity is a well-known risk factor for the development of secondary complications such as type 2 diabetes. However, only a part of the obese population develops secondary metabolic disorders. Here, we identify the transcription factor retinoid-related orphan receptor gamma (ROR?) as a negative regulator of adipocyte differentiation through expression of its newly identified target gene matrix metalloproteinase 3. In vivo differentiation of adipocyte progenitor cells from Ror?-deficient mice is enhanced and obese Ror??/? mice show decreased adipocyte sizes. These small adipocytes are highly insulin sensitive, leading to an improved control of circulating free fatty acids. Ultimately, Ror??/? mice are protected from hyperglycemia and insulin resistance in the state of obesity. In adipose stromal-vascular fraction from obese human subjects, Ror? expression is correlated with adipocyte size and negatively correlated with adipogenesis and insulin sensitivity. Taken together, our findings identify ROR? as a factor, which controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. ROR? might therefore serve as a novel pharmaceutical target to treat obesity-associated insulin resistance.
Notas:Gesehen am 17.08.2022
Descripción Física:Online Resource
ISSN:1757-4684
DOI:10.1002/emmm.201100172