"given that exercise induces myonectin expression in skeletal muscle, we next addressed whether short- and long-term changes in nutritional/metabolic state also regulate myonectin expression and circulating levels. surprisingly, an overnight fast greatly suppressed myonectin expression, but a 2-h refeeding period (following an overnight fast) dramatically up-regulated its mrna expression in skeletal muscle. intriguingly, refeeding induced myonectin mrna expression to a much greater extent in soleus than in plantaris muscle fiber of both male and female mice (data not shown), suggesting that myonectin expression may be regulated differentially depending on muscle fiber type. consistent with the mrna data, fasting reduced, but refeeding substantially increased, circulating levels of myonectin... as compared with mice fed an isocaloric matched low-fat diet, mice fed a high-fat diet had lower myonectin mrna and serum levels, suggesting that obesity-induced alteration in energy balance may be linked to dysregulation of myonectin-mediated processes in the obese state... a relatively modest rise in serum myonectin levels was sufficient to lower (by >30%) nonesterified free fatty acid (nefa) levels over time relative to vehicle-injected controls. however, no significant difference was observed in serum triacylglycerol levels between the two groups of mice. these data suggest a potential role of myonectin in regulating systemic fatty acid metabolism... treatment of adipocytes with recombinant myonectin (5 micrograms/ml) also enhanced fatty acid uptake to the same extent as insulin... to determine whether myonectin-mediated enhancement of lipid uptake is specific to adipocytes, we also tested the effect of myonectin on lipid uptake in rat h4iie hepatocytes. we observed a modest (>25%) but consistent increase in fatty acid uptake into hepatocytes stimulated with myonectin (5 micrograms/ml), an effect similar to cells treated with a saturating dose of insulin (50 nm)... together, these results indicate that myonectin promotes lipid uptake into adipocytes and hepatocytes via transcriptional up-regulation of genes involved in fatty acid uptake...