Study summary · research use only
[Pharmacological Activation of ERRα/β/γ as an Exercise Mimetic: Potential Therapeutic Applications]
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This systematic review (2020-2024 literature) covers experimental studies in animals and cell models (species not specified) examining pharmacological activation of estrogen-related receptors ERRα/β/γ as exercise mimetics, focusing on the synthetic pan-agonists SLU-PP-332 and SLU-PP-915. The abstract reports that pan-ERR agonists induced a gene-expression program resembling acute aerobic exercise, dependent on ERRα, including activation of Ddit4 and Slc25a25, and were associated with increased fatty acid oxidation, more type IIa muscle fibers, and improved endurance in the reviewed studies. SLU-PP-332 and SLU-PP-915 were linked to reduced adiposity, improved glycemic control, and increased basal energy expenditure in obesity models, and to restored mitochondrial function and reduced inflammation in aging kidneys. The authors state clinical trials are needed to assess these agents in humans.
Abstract
Physical inactivity contributes to the development of chronic diseases. Activation of orphan nuclear receptors estrogen-related receptors (ERRα/β/γ) has emerged as a molecular strategy to mimic exercise-induced benefits. To systematically review the current evidence on the physiological, molecular, and clinical effects of synthetic pan-ERR agonists, especially SLU-PP-332 and SLU-PP-915, in preclinical models and their potential as exercise mimetics. A systematic review of scientific literature from 2020 to 2024 was conducted, including experimental studies in animals and cell models. Molecular mechanisms, effects on energy metabolism, muscle function, renal aging, and metabolic syndrome were analyzed. Pan-ERR agonists induce a gene expression program like acute aerobic exercise, dependent on ERRα, including activation of Ddit4 and Slc25a25. They enhance fatty acid oxidation, increase type IIa muscle fibers (oxidative-glycolytic, with mixed substrate utilization including fatty acids and glucose), and improve endurance. SLU-PP-332 and SLU-PP-915 reduce adiposity, improve glycemic control, and increase basal energy expenditure in obesity models, without evident toxicity. Additionally, they restore mitochondrial function and reduce inflammation in aging kidneys. Pharmacological activation of ERRα/β/γ is a promising strategy as an exercise mimetic, with potential therapeutic applications in metabolic diseases, aging, and muscle-related conditions. Clinical trials are needed to confirm their efficacy and safety in humans.
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