Methods and Compositions for Modulating Necdin Function

Description: The most common fat cells are white adipose tissue (WAT) cells, which have a thin ring of cytoplasm surrounding a lipid or fat droplet. WAT is found underneath the skin and provides heat insulation, cushioning against shock and jarring, and energy reserves. An average lean person has roughly 20 to 40 billion WAT cells, and an obese person can have up to ten times more WAT than the average lean person. The less common fat cells are the brown adipose tissue (BAT) cells. Energy expenditure for thermogenesis in BAT serves either to maintain body temperature in the cold or to waste food energy. It has roles in thermal balance and energy balance, and when defective, is usually associated with obesity. BAT is usually atrophied in obese animals. The importance of BAT in overall energy homeostasis is underscored by the finding that ablation of BAT in mice results in severe obesity accompanied by insulin resistance, hyperglycemia, hyperlipidemia, and hypercholesterolemia. One potential avenue for therapeutic modulation of a person’s weight might be to alter the balance between WAT and BAT cells. Clinical & Commercial Utility: Using microarray analysis, the inventors have discovered a number of genes and ESTs whose expression in preadipocytes correlates with the ultimate ability of the cells to differentiate. Specifically, it was found that the protein necdin, a growth suppressor expressed in postmitotic brain neurons, was markedly increased in cells that were incapable of differentiation, and that knockdown of necdin function restored brown adipogenesis. The invention therefore comprises methods for decreasing fat stores or treating weight gain, by administering an inhibitor of necdin, or otherwise downregulating necdin activity, in order to promote BAT differentiation and inhibit WAT adipogenesis. The invention also comprises methods of drug screening and diagnostics based on necdin’s role in BAT differentiation. A U.S. patent application claiming this invention has been filed. The research underlying this invention has been published (Tseng, et al., 2005, Nature Cell Biology 7(6):601-611).

Type of Offer: Licensing

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