**11. Other conditions in which circulating CNP levels are affected**

CNP regulates fat metabolism in adipogenic tissue, and adipogenic CNP transgenic mice is resistant to obesity when fed by high fat content. Natriuretic peptides regulate intracellular cGMP and phosphorylated vasodilator-stimulated phosphoprotein (VASP). Adipogenic CNP transgenic mice showed a decrease in fat weight and adipocyte hypertrophy and increases in fatty acid β-oxidation, lipolysis-related gene expression, and energy expenditure during high fat diet (HFD)-induced obesity. Furthermore it seems like CNP overexpression diminished the inflammatory activity in adipogenic tissue. Adipogenic cell CNP transgenic mice were reported to have significantly decreased gene expression of TNF-α, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and F4/80 in mature adipocytes [98]. Adipogenic CNP transgenic mice also developed better glucose tolerance and insulin sensitivity, which were found to be associated with enhanced insulin-stimulated Akt phosphorylation. It was suggested that CNP overexpression in adipocytes protects against adipocyte hypertrophy, excess lipid metabolism, inflammation, and decreased insulin sensitivity during HFD-induced obesity. An earlier report also suggested that overexpression of endothelialspecific CNP overexpression protects against visceral adipose tissue hypertrophy, systemic inflammation, and insulin resistance during the development of obesity due to the feeding of a high-fat diet (HFD) [99]. Overall current knowledge suggests that natriuretic peptides are new pathways controlling human adipose tissue lipolysis operating via a cGMP-dependent pathway.

One of the intriguing studies is one that examined serum levels of 53 patients with Behçet's disease and showed that all patients with active disease had lower levels of CNP indicating its suppression by inflammatory disease activity [100]. Thus, there is evidence that during chronic inflammatory diseases CNP serum levels might be suppressed which can impact the skeletal growth if the individuals affected have open growth plates and ongoing longitudinal growth process.
