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Adipose Precursor HO-1 determines healthy visceral adipose tissue expansion during obesity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE80148 | GEO | 2017/03/08

SECONDARY ACCESSION(S): PRJNA318034

REPOSITORIES: GEO

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Adipose Precursor HO-1 prevents healthy visceral adipose tissue expansion during obesity[II]

Project description:Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors (APs), however, the underlying molecular mechanisms remain unclear. Here, we identify Heme Oxygenase-1 (HO-1) as selectively being upregulated in the AP fraction of WAT, upon high-fat diet (HFD) feeding. Specific conditional deletion of HO-1 in APs of Hmox1fl/fl-Pdgfra Cre mice enhanced HFD-dependent visceral AP proliferation and differentiation, upstream of Cebpα and PPARγ. Opposite effects on human preadipocyte proliferation and differentiation in vitro were observed following HO-1 overexpression. Mechanistically, HO-1 acts upstream of AKT2 via ROS thresholding in mitochondria. Deletion of HO-1 in APs is sufficient to lower blood glucose, insulin and free fatty acid levels as well as liver steatosis during obesity, an effect not seen when HO-1 was conditionally deleted at later stages of adipogenesis using AdipoQ-Cre. Together, our data identify HO-1 as a diet-induced regulator limiting visceral adipose tissue hyperplasia during obesity.

2017-03-08 | GSE80147 | GEO

Adipose Precursor HO-1 prevents healthy visceral adipose tissue expansion during obesity [I]

2017-03-08 | GSE80146 | GEO