"we provide the first characterization of myonectin, with in vitro and in vivo evidence that it is a novel myokine with important metabolic function. unlike the other ctrps characterized to date, myonectin (ctrp15) is expressed and secreted predominantly by skeletal muscle... (our) results suggest that myonectin is a nutrient-responsive metabolic regulator secreted by skeletal muscle in response to changes in cellular energy state resulting from glucose or fatty acid fluxes. many metabolically relevant secreted proteins (e.g. adiponectin, leptin, resistin, and rbp) and the signaling pathways they regulate in tissues are known to be dysregulated in the condition of obesity. the reduction in expression and circulating levels of myonectin in the obese state may represent yet another component of the complex metabolic circuitry dysregulated by excess caloric intake. although exercise has long been known to have profound positive impacts on systemic insulin sensitivity and energy balance, the underlying mechanisms remain incompletely understood. that voluntary exercise dramatically increases the expression and circulating levels of myonectin to promote fatty acid uptake into cells may underlie one of the beneficial effects of physical exercise... a modest rise in the circulating levels of myonectin resulting from recombinant protein administration is sufficient to lower serum nefa without altering serum triglyceride levels. unlike ctrp1, ctrp3 and ctrp12, injection of recombinant myonectin into mice appears to have no glucose-lowering effect. reduction in circulating nefa is not due to suppression of adipose tissue lipolysis; rather, it results from increased fatty acid uptake by adipocytes and hepatocytes. although the myonectin-mediated enhancement of lipid uptake in vitro appears modest (25–50%), in fact, the magnitude of this effect is comparable with cells stimulated with 50 nm insulin, a saturating dose that leads to maximum increase in fatty acid uptake... in accordance with myonectin mediating its metabolic effect through a transcriptional mechanism, a reduction in circulating nefa in mice occurred only 2 h after recombinant protein injection, a lag period presumably required for mrna and protein synthesis."