Irisin, out-membrane part of fibronectin type III domain–containing 5 protein (FNDC5), was activated by Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) during physical exercise in skeletal muscle tissues. Most studies have reported that the concentration of irisin is highly associated with health status. For instance, the level of irisin is significantly lower in patients with obesity, osteoporosis/fractures, muscle atrophy, Alzheimer’s disease, and cardiovascular diseases (CVDs) but higher in patients with cancer. Irisin can bind to its receptor integrin αV/β5 to induce browning of white fat, maintain glucose stability, keep bone homeostasis, and alleviate cardiac injury. However, it is unclear whether it works by directly binding to its receptors to regulate muscle regeneration, promote neurogenesis, keep liver glucose homeostasis, and inhibit cancer development. Supplementation of recombinant irisin or exercise-activated irisin might be a successful strategy to fight obesity, osteoporosis, muscle atrophy, liver injury, and CVDs in one go. Here, we summarize the publications of FNDC5/irisin from PubMed/Medline, Scopus, and Web of Science until March 2022, and we review the role of FNDC5/irisin in physiology and pathology.

As common progenitor cells of osteoblasts and adipocytes, bone marrow mesenchymal (stromal) stem cells (BMSCs) play key roles in bone homeostasis, tissue regeneration, and global energy homeostasis; however, the intrinsic mechanism of BMSC differentiation is not well understood. Plasticity in energy metabolism allows BMSCs to match the divergent demands of osteo-adipogenic differentiation. Targeting BMSC metabolic pathways may provide a novel therapeutic perspective for BMSC differentiation unbalance related diseases. This review covers the recent studies of glucose, fatty acids, and amino acids metabolism fuel the BMSC differentiation. We also discuss recent findings about energy metabolism in BMSC differentiation. Glucose, fatty acids, and amino acids metabolism provide energy to fuel BMSC differentiation. Moreover, some well-known regulators including environmental stress, hormone drugs, and biological and pathological factors may also influence BMSC differentiation by altering metabolism. This offers insight to the significance of metabolism on BMSC fate determination and provides the possibility of treating diseases related to BMSC differentiation, such as obesity and osteoporosis, from a metabolic perspective.