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Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice

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

ORGANISM(S): Mus musculus

PROVIDER: GSE92607 | GEO | 2017/02/27

SECONDARY ACCESSION(S): PRJNA358145

REPOSITORIES: GEO

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Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice [ChIP-Seq]

Project description:Obesity causes insulin resistance, and PPARγ ligands like rosiglitazone (rosi) are insulin-sensitizing, yet mechanisms remain unclear. High fat diet (HFD) induced obesity has major effects on visceral epididymal adipose tissue (eWAT) of C57BL/6 (B6) mice, and here we report altered activity of gene regulatory elements with changes in PPARγ genome-wide occupancy. Treatment with rosi restored insulin sensitivity, yet surprisingly had little effect on eWAT, leading us to consider the subcutaneous inguinal fat (iWAT). In this depot, rosi markedly induced molecular signatures of brown fat including the key thermogenic gene Ucp1. Obesity-resistant 129S1/SvImJ (129) mice showed this degree of iWAT browning even in the absence of rosi. Remarkably, the 129 Ucp1 locus had increased PPARγ binding and gene expression that was preserved in B6x129 F1 intercross iWAT, with imbalance favoring the 129-derived alleles showing a cis-acting genetic difference. Thus, B6 mice have a genetic defect in Ucp1 expression. However, imbalanced expression favoring 129 over B6 was nearly lost when Ucp1 was activated by rosi, or by iWAT browning in cold-exposed or young mice. These results provide a novel framework for understanding how environmental influences like drugs can rescue genetically determined disease phenotypes by affecting the epigenome.

2017-02-27 | GSE92606 | GEO

Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice [RNA-Seq]

2017-02-27 | GSE91067 | GEO

Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice

Project description:Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice

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Prenatal PPAR? activation by clofibrate increases subcutaneous fat browning in male C57BL/6J mice fed a high-fat diet during adulthood.

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miRNA-32 Drives Brown Fat Thermogenesis and Trans-activates Subcutaneous White Fat Browning in Mice.

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