title: 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 (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 Rorγ-deficient mice is enhanced and obese Rorγ(-/-)  mice show decreased adipocyte sizes. These small adipocytes are highly insulin sensitive, leading to an improved control of circulating free fatty acids. Ultimately, Rorγ(-/-)  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.
authors.affiliation: ETH Zürich, Institute of Food Nutrition and Health, Schwerzenbach, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Meissburger
authors.forename: Jozef
authors.initials: J
authors.lastname: Ukropec
authors.forename: Eva
authors.initials: E
authors.lastname: Roeder
authors.forename: Nigel
authors.initials: N
authors.lastname: Beaton
authors.forename: Matthias
authors.initials: M
authors.lastname: Geiger
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Burcak
authors.initials: B
authors.lastname: Civan
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Daniela
authors.initials: D
authors.lastname: Gasperikova
authors.forename: Gottfried
authors.initials: G
authors.lastname: Rudofsky
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D048429:Cell Size; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D007328:Insulin; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D019278:Matrix Metalloproteinase 3