seldin, peterson, byerly, wei and wong clarify that most myokines are also secreted by non-muscle cells. in 2012, they reported: "the expression of all myokines described to date is not restricted to skeletal muscle; they are generally expressed by a variety of cell types, and most are, in fact, expressed at much higher levels by nonmuscle tissues. prior to (our) study, no myokine has been discovered to be preferentially expressed by skeletal muscle. while characterizing the metabolic function of the c1q/tnf-related protein (ctrp) family of proteins we recently uncovered, we identified myonectin (ctrp15) as a novel member of the family on the basis of sequence homology in the shared c1q domain, the signature that defines this protein family... (myonectin) is a novel nutrient-responsive myokine secreted by skeletal muscle to regulate whole-body fatty acid metabolism... circulating levels of myonectin were tightly regulated by the metabolic state; fasting suppressed, but refeeding dramatically increased, its mrna and serum levels. although mrna and circulating levels of myonectin were reduced in a diet-induced obese state, voluntary exercise increased its expression and circulating levels. accordingly, myonectin transcript was up-regulated by compounds (forskolin, epinephrine, ionomycin) that raise cellular camp or calcium levels... in vitro results of myonectin expression in myotubes suggest that exercise-induced rises in intracellular calcium levels may also up-regulate myonectin expression in intact skeletal muscle... consistent with enhanced mrna expression in skeletal muscle of mice subjected to voluntary exercise, circulating levels of myonectin also increased, suggesting a potential role of myonectin in exercise-induced physiology.