PDE4 inhibition is anabolic for muscles by inhibiting mTORC1/FoxO transcription factor/E3 ubiquitin ligase axis.
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PDE4 is mainly expressed in skeletal muscles. Chronic activation of mTORC1 by exercise and aging upregulates catabolic factors, limiting muscular development. PDE4 inhibitors counteract this and can be used as anabolic agents.
Relevant research:
The phosphodiesterase-4 inhibitor roflumilast reverts proteolysis in skeletal muscle cells of patients with COPD cachexia
https://pubmed.ncbi.nlm.nih.gov/29648516/
Impaired cAMP–PKA–CREB1 signalling drives mitochondrial dysfunction in skeletal muscle during cancer cachexia
https://www.nature.com/articles/s42255-025-01397-5#Sec10
Phosphodiesterase 4 inhibition restrains muscle proteolysis in diabetic rats by activating PKA and EPAC/Akt effectors and inhibiting FoxO factors.
https://www.repositorio.ufop.br/items/1bd5a6b9-2627-467f-8ca8-ffac2170b4fa
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