Induction of UCP1 and thermogenesis by a small molecule via AKAP1/PKA modulation.

ABSTRACT: Strategies to increase energy expenditure are an attractive approach to reduce excess fat storage and body weight to improve metabolic health. In mammals, uncoupling protein-1 (UCP1) in brown and beige adipocytes uncouples fatty acid oxidation from ATP generation in mitochondria and promotes energy dissipation as heat. We set out to identify small molecules that enhance UCP1 levels and activity using a high-throughput screen of nearly 12,000 compounds in mouse brown adipocytes. We identified a family of compounds that increase Ucp1 expression and mitochondrial activity (including un-coupled respiration) in mouse brown adipocytes and human brown and white adipocytes. The mechanism of action may be through compound binding to A kinase anchoring protein (AKAP) 1, modulating its localiz

SUBMITTER: Vergnes L 

PROVIDER: S-EPMC7606676 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature