1. Human but not mouse adipogenesis is critically dependent on LMO3.
- Author
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Lindroos J, Husa J, Mitterer G, Haschemi A, Rauscher S, Haas R, Gröger M, Loewe R, Kohrgruber N, Schrögendorfer KF, Prager G, Beck H, Pospisilik JA, Zeyda M, Stulnig TM, Patsch W, Wagner O, Esterbauer H, and Bilban M
- Subjects
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 physiology, Adaptor Proteins, Signal Transducing genetics, Adipocytes pathology, Adipogenesis genetics, Adult, Animals, Case-Control Studies, Cell Differentiation physiology, Cells, Cultured, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Experimental physiopathology, Disease Models, Animal, Female, Glucocorticoids physiology, Humans, Intra-Abdominal Fat pathology, LIM Domain Proteins genetics, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, SCID, Middle Aged, Obesity pathology, PPAR gamma physiology, Up-Regulation genetics, Adaptor Proteins, Signal Transducing physiology, Adipogenesis physiology, Intra-Abdominal Fat physiology, LIM Domain Proteins physiology, Obesity physiopathology, Up-Regulation physiology
- Abstract
Increased visceral fat is associated with a high risk of diabetes and metabolic syndrome and is in part caused by excessive glucocorticoids (GCs). However, the molecular mechanisms remain undefined. We now identify the GC-dependent gene LIM domain only 3 (LMO3) as being selectively upregulated in a depot-specific manner in human obese visceral adipose tissue, localizing primarily in the adipocyte fraction. Visceral LMO3 levels were tightly correlated with expression of 11β-hydroxysteroid dehydrogenase type-1 (HSD11B1), the enzyme responsible for local activation of GCs. In early human adipose stromal cell differentiation, GCs induced LMO3 via the GC receptor and a positive feedback mechanism involving 11βHSD1. No such induction was observed in murine adipogenesis. LMO3 overexpression promoted, while silencing of LMO3 suppressed, adipogenesis via regulation of the proadipogenic PPARγ axis. These results establish LMO3 as a regulator of human adipogenesis and could contribute a mechanism resulting in visceral-fat accumulation in obesity due to excess glucocorticoids., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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