Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells

Figure 3 Key regulators of the browning process and their action mechanisms. Browning is induced by sympathetic nervous system (SNS)-independent or SNS-dependent signals. These signals sometimes synergistically or competitively influence the activation of browning of subcutaneous white adipose tissue (sWAT). Irisin is a newly discovered myokine and is released by skeletal muscle during exercise. Irisin induces the browning process of sWAT. Fibroblast growth factor-21 (FGF21), a hormonal factor from the liver, directly activates the thermogenic process via interaction with the FGF receptor/β-Klotho (KLB) complex. The norepinephrine secreted by the SNS in response to thermogenic stimuli induces the activation of adrenergic receptor(s). The adrenergic receptor-mediated signal increases the level of intracellular cAMP and activates cAMP-dependent protein kinase A (PKA). Subsequently, PKA activates p38 MAP kinase (p38 MAPK) and 5’-deiodinase 2 (Dio2), which catalyzes the conversion of thyroxine (T4) into the active form 3,5,3’-tri-iodothyronine (T3). Then, it ultimately induces the gene process for thermogenic activation. Natriuretic peptides (NPs) originating from the heart activate the thermogenic process through binding to the NP receptor, activation of protein kinase G (PKG) and the subsequent activation of p38 MAPK and NPR. NPR: Natriuretic peptides receptor; TAG: Triacylglycerol; FA: Fatty acid.