Fat Tissue Protects Muscle: A Protein Secreted by NAD+ Signaling Suppresses Muscle Wasting

A mouse study has suggested that fat tissue is not just an energy store but an organ that sends signals to protect muscle. Researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College reported in Cell Metabolism that Serpina3n, a protein secreted from fat tissue in response to the coenzyme NAD+, suppresses muscle atrophy.

A signal from fat to muscle between organs

The researchers traced through which pathway the effect of NAD+ supplementation in preventing muscle loss arises. When NAD+ rose in fat tissue, the transcription factor STAT1 was activated and expression of the Serpina3n gene switched on, and the secreted Serpina3n protected muscle in several muscle atrophy models, including aging, limb immobilization (disuse) and cancer cachexia. Inside muscle, Serpina3n maintained levels of pyruvate carboxylase, supporting TCA cycle replenishment (anaplerosis), oxidative metabolism and protein synthesis.

These results show that an inter-organ axis (adipose-muscle axis) exists through which metabolic state affects muscle health by way of fat tissue. It could be a clue to the link between muscle loss in older age and metabolic health.

All experiments were done in mice, and it has not been confirmed whether the corresponding human protein plays the same role. The results should not be read as supporting a clinical effect of NAD+ supplementation.