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In search of a lean gene

Independent research groups have discovered novel therapeutic targets in the battle of the bulge. By altering the expression of a single -- albeit different gene, Drs. Roger Davis (UMASS Medical School, USA) and Ying-Hue Lee (Academia Sinica, Taiwan) have succeeded in creating two different strains of transgenic mice that don't gain weight, even when fed fat-laden, high calorie diets.

Their reports will be published in the August 15th edition of Genes & Development.

Living longer, weighing less

Dr. Ying-Hue Lee and colleagues at Academia Sinica took a different approach towards the obesity epidemic, analyzing the effects of C/EBP gene replacement in mice. The C/EBP protein family consists of 5 members, 3 of which (alpha, beta, and delta) have established roles in promoting adipogenesis (fat cell differentiation). The researchers were specifically interested in determining the physiological impact of replacing the C/EBPalpha gene with the C/EBPbeta gene.

"No doubt, C/EBPalpha is very important for life as indicated by many excellent studies related to its physiological function. Still, we wondered that its cousin, C/EBPbeta, might do the job well as well if given a chance," explains Dr. Lee.

Dr. Lee and colleagues utilized an existing strain of mice that contains the alpha-to-beta gene substitution, referred to in the paper as "beta/beta mice." They found that beta/beta mice not only live an average of 5 months longer than wild-type mice, but are markably leaner, apparently burning fat at a much higher rate than normal mice.

Dr. Lee and colleagues observed that despite their svelte appearance, beta/beta mice actually eat more food and are no more active than their genetically normal littermates. In search of the cause of this revved-up metabolism, Dr. Lee's team found that the white adipose tissue, which is normally reserved for fat storage, had actually been converted into fat burning cells in beta/bet
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Contact: Heather Cosel-Pieper
coselpie@cshl.edu
Cold Spring Harbor Laboratory
1-Aug-2004


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