Inhibition of Sirt$ for treatment of obesity and ehancing fat metabolism

Summary A method of screening for compounds that modulate SIRT4 fatty acid oxidation activity.

SIRT4 is a mitochondrial protein that plays a central role in regulating amino acid stimulated insulin secretion (AASIS) in pancreatic ?-cells by inhibiting glutamate dehydrogenase and impacting fatty acid oxidation. Alterations in lipid metabolism occur during aging and metabolic stress, and are therefore implicated in the pathogenesis of age-related and metabolic diseases.

Applications Data from SIRT4 KO mice show that loss of SIRT4 function alters fatty acid synthesis and metabolism. High-fat diets fed to wild-type and SIRT4 KO mice indicated that SIRT4 KO mice gained only 11% of their body weight, compared to 25% in the wild-type. SIRT4 KO mice fed a high fat diet gained weight on par with wild-type mice fed a low-fat diet.

Compounds that down-regulate SIRT4 activity may be used to treat obesity, while compounds that up-regulate SIRT4 activity may be used in the treatment of AIDS and Chemotherapy associated cachexia. For Further Information Please Contact the Director of Business Development Michal Preminger Email: michal_preminger@hms.harvard.edu Telephone: (617) 432-0920

Inventor(s): Haigis, Marcia

Type of Offer: Licensing



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