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Acute treatment with chemical PPARGC1a1 activators in brown fat cells

ABSTRACT: The peroxisome proliferator-activated receptor-coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation has been suggested to be beneficial for systemic metabolism. Pharmacological PGC-1α1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1α1 is a transcriptional coactivator with no known ligand-binding activities. Importantly, PGC-1α1 activation is regulated by several mechanisms but protein stabilization is a limiting step as the protein has a short half-life under unstimulated conditions. We designed a cell-based high-throughput system to identify stabilizers of PGC-1α1 protein. Positive hits were tested for their ability to induce endogenous PGC-1α1 protein accumulation and activate target gene expression in brown adipocytes. Selected compounds were analyzed for their effects on global gene expression in brown adipocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE107630 | GEO | 2018/02/02

REPOSITORIES: GEO

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