Human but Not Mouse Adipogenesis Is Critically Dependent on LMO3

Abstract

SummaryIncreased 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.

LipiD-QuanT: a novel method to quantify lipid accumulation in live cells

“…1). The gene expression changes were consistent with previously published data confi rming that SGBS preadipocyte differentiation is a reproducible model for the study of human adipogenesis ( 12,(37)(38)(39)(40).…”

Metabolic comorbidities in Cushing's syndrome

“…LMO3 has been recently demonstrated to be upregulated by GCs, to correlate with 11BHSD1 levels and to promote adipogenesis via increasing PPARg tone in human VAT (90). As LMO3 is not expressed in rodent visceral tissue, this mechanism could also explain the well-known striking difference in GC-induced visceral adiposity in humans and mice.…”

Dexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity

“…Very recently, Lindroos et al (24) reported that the adaptor protein LMO3 is induced by glucocorticoids and modulates adipogenesis in human but not mouse tissues. Whether LMO3 and Dexras1 interface in regulating adipogenesis is unclear.…”