Open AccessAdipogenesis and insulin sensitivity in obesity are regulated by retinoid‐related orphan receptor gamma
Author(s) -
Meissburger Bettina,
Ukropec Jozef,
Roeder Eva,
Beaton Nigel,
Geiger Matthias,
Teupser Daniel,
Civan Burcak,
Langhans Wolfgang,
Nawroth Peter P.,
Gasperikova Daniela,
Rudofsky Gottfried,
Wolfrum Christian
Publication year - 2011
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201100172
Subject(s) - adipogenesis , adipocyte , endocrinology , medicine , insulin resistance , stromal vascular fraction , orphan receptor , adipose tissue , biology , insulin , transcription factor , biochemistry , gene
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 (RORγ) 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 γ‐deficient mice is enhanced and obese Ror γ −/− mice show decreased adipocyte sizes. These small adipocytes are highly insulin sensitive, leading to an improved control of circulating free fatty acids. Ultimately, Ror γ −/− mice are protected from hyperglycemia and insulin resistance in the state of obesity. In adipose stromal‐vascular fraction from obese human subjects, Rorγ expression is correlated with adipocyte size and negatively correlated with adipogenesis and insulin sensitivity. Taken together, our findings identify RORγ as a factor, which controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. RORγ might therefore serve as a novel pharmaceutical target to treat obesity‐associated insulin resistance.