Synthetic ERRalpha/beta/gamma Agonist Induces an ERRalpha-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity

This preclinical study investigated SLU-PP-332, a synthetic agonist of estrogen-related receptors (ERRalpha/beta/gamma), evaluating its ability to induce metabolic responses similar to aerobic exercise in mice. Researchers from the University of Florida and collaborators used gene expression analyses, muscle histology, and functional endurance tests.

The compound demonstrated a remarkable ability to activate an acute aerobic exercise genetic program in an ERRalpha-dependent manner. In treated mice, there was a significant increase in oxidative type IIa skeletal muscle fibers, which are fast-twitch fibers with high aerobic capacity. Concurrently, improved mitochondrial function and increased mitochondrial biogenesis were observed in skeletal muscle.

• Treadmill exercise capacity improved significantly in treated animals
• The gene expression profile faithfully mimicked the pattern observed after real aerobic exercise
• The effect was predominantly mediated by ERRalpha activation, as confirmed in knockout models

SLU-PP-332 gained media attention as a potential "exercise pill," although the researchers emphasized that the compound is a research tool. The findings suggest that the ERR pathway may be a promising pharmacological target for conditions where physical exercise is limited, such as neuromuscular diseases or prolonged immobilization.