( rR knockout mice the antagonist-treate...)Elixir Pharmaceuticals Presents Preclinical Data Highlighting Its,Ghrelin Antagonist Program at the American Diabetes Association's,Annual Meeting,Health

rR knockout mice, the antagonist-treated mice on a high-fat diet showed decreased body weight, as well as improved glucose and insulin control compared to the mice treated with vehicle. In addition, GhrR antagonist treatment resulted in a significant reduction in liver fat content and improved liver function (as measured by liver enzyme levels) relative to the vehicle-treated mice. The results demonstrate that GhrR antagonist treatment of normal high fat-fed mice completely recapitulates the phenotype of the high fat fed GhR knockout mice.

A second poster presentation explored whether ghrelin exerts a direct effect on adipocytes (fat cells) and if the effect is mediated through ghrelin receptor mRNA expression in these cells. To assess this, the scientists first examined ghrelin signaling by measuring insulin sensitivity in mouse adipocyte cell lines that were treated with ghrelin for four days. Scientists also assessed the expression of GhrR mRNA in adipose tissue, isolated adipocytes from mice, and the mouse adipocyte cell-line. The results showed GhrR was detected in the isolated adipocytes and mouse adipocyte cell lines, suggesting ghrelin acts directly through its receptor on adipocytes to regulate energy homeostasis. Moreover, the reduction of insulin signaling in adipocytes by chronic ghrelin treatment provides a possible mechanism for increased insulin sensitivity in GhrR knockout mice.

"Ghrelin antagonism represents one of the most fascinating and promising therapeutic approaches in diabetes and obesity research today because of its integral role in regulating metabolism. These preclinical data validate our hypothesis that by inhibiting ghrelin's normal function with a potent, small molecule therapeutic, one can effectively improve glucose control, manage body weight, and regulate metabolism. Should this approach be confirmed in clinical testing, we believe ghrelin inhibition could represent a significant advance for the treatment of serious a
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