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Ileal FXR-FGF15/19 signaling activation improves skeletal muscle loss in aged mice
Yixuan Qiu1, Jiaming Yu1, Xueying Ji1
1Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200000, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200000, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200000, China.
Abstract:
Sarcopenia is the age-related decrease in skeletal muscle mass, and current therapies for this disease are ineffective. We previously showed that ileal farnesoid X receptor (FXR)-fibroblast growth factor 15/19 (FGF15/19) signaling acts as a regulator of gut microbiota to mediate host skeletal muscle. However, the therapeutic potential of this pathway for sarcopenia is unknown. This study showed that ileal FXR-FGF15/19 signaling was downregulated in older men and aged male mice due to changes in the gut microbiota and microbial bile acid metabolism during aging. In addition, the intestine-specific FXR agonist fexaramine increased skeletal muscle mass and improve muscle performance in aged mice. Ileal FXR activation increased skeletal muscle protein synthesis in a FGF15/19-dependent way, indicating that ileal FXR-FGF15/19 signaling is a potential therapeutic target for sarcopenia.
