Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.

ABSTRACT:

Objective

The peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation is potentially 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 properties. While, PGC-1α1 activation is regulated by several mechanisms, protein stabilization is a crucial limiting step due to its short half-life under unstimulated conditions.

Methods

We designed a cell-based high-throughput screening system to identify PGC-1α1 protein stabilizers. Po

SUBMITTER: Pettersson-Klein AT 

PROVIDER: S-EPMC5870114 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature