Steroid receptor coactivators: servants and masters for control of systems metabolism

• SRCs are required for diverse metabolic processes.
• SRCs impact metabolic systems physiology.
• SRC dysfunction confers metabolic pathophysiology.
• SRCs bridge anabolic and catabolic functions for the maintenance of energy homeostasis.

Coregulator recruitment to nuclear receptors (NRs) and other transcription factors is essential for proper metabolic gene regulation, with coactivators enhancing and corepressors attenuating gene transcription. The steroid receptor coactivator (SRC) family is composed of three homologous members (SRC-1, SRC-2, and SRC-3), which are uniquely important for mediating steroid hormone and mitogenic actions. An accumulating body of work highlights the diverse array of metabolic functions regulated by the SRCs, including systemic metabolite homeostasis, inflammation, and energy regulation. We discuss here the cooperative and unique functions among the SRCs to provide a comprehensive atlas of systemic SRC metabolic regulation. Deciphering the fractional and synergistic contributions of the SRCs to metabolic homeostasis is crucial to understanding fully the networks underlying metabolic transcriptional regulation.