N-substituted Phenylbenzamides of the Niclosamide chemotype attenuate obesity related changes in high fat diet fed mice
Results are encouraging
In this manuscript, submitted to PLOS One, we describe that Niclosamide, an FDA-approved anthelmintic drug, and its phenylbenzamide analogs have efficacy in murine models of diet induced obesity characterized by attenuation of the prominent fatty liver disease phenotype and improved glucose metabolism. While the exact mechanism(s) underlying these changes remains unclear, the ability to uncouple oxidative phosphorylation leading to increased energy expenditure and lipid metabolism or attenuation of PKA mediated glucagon signaling in the liver have been proposed.
We developed a novel hepatic steatosis assay that involves stimulating human liver cells to accumulate fat and relies on high content automated imaging to count and score cells for the extent of steatosis.
A positive result
We demonstrated the Niclosamide improves glucose tolerance in obese diabetic mice, stimulates AMPK activation and decreases fatty acid synthase and carbonic anhydrase III.