Loss of skeletal muscle mass is a significant contributor to frailty and disability, yet the mechanisms by which systemic metabolic cues protect muscle integrity are not fully understood. This study identifies Serpina3n, an adipose-derived adipokine, as a crucial mediator of the protective effects of nicotinamide adenine dinucleotide (NAD+) supplementation against muscle atrophy.
In the context of aging, disuse, and cancer cachexia, the elevation of NAD+ in adipose tissue activates the signal transducer and activator of transcription (STAT)1-dependent transcription of Serpina3n. This process leads to the systemic release of Serpina3n, which in turn provides muscle protection. The findings suggest that Serpina3n plays a vital role in preserving the protein level of pyruvate carboxylase in muscle, thereby promoting anaplerosis, oxidative metabolism, and protein synthesis.
These results define an NAD+-responsive adipose-to-muscle signaling axis that connects metabolic status to tissue preservation. This systemic mechanism highlights the importance of inter-organ communication in maintaining muscle integrity and suggests potential strategies to counteract muscle degeneration.
What this study does not show
This study does not provide direct evidence of clinical outcomes in humans related to NAD+ supplementation or Serpina3n application for muscle atrophy.
Evidence scorecard
- Analytic validity: Not established
- Clinical validity: Not established
- Clinical utility: Not established
The evidence class is primary_research and the human status is unclassified.