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Papers In Press, published online ahead of print August 27, 2004
J. Biol. Chem, 10.1074/jbc.M403855200
Submitted on April 7, 2004
Revised on August 27, 2004
Accepted on August 27, 2004

Desnutrin, an adipocyte gene encoding a novel patatin-domain containing protein, is induced by fasting and glucocorticoids. Ectopic expression of desnutrin increases triglyceride hydrolysis

Josep A. Villena, Suheeta Roy, Eszter Sarkadi-Nagy, KeeHong Kim, and HeiSook Sul

Nutritional Sciences, University of California, Berkeley, CA 94720

Corresponding Author: hsul{at}nature.berkeley.edu

We have used rat cDNA microarrays to identify adipocyte-specific genes that could play an important role in adipocyte differentiation or function. Here, we report the cloning and identification of a 2.0 kb mRNA coding for a putative protein that we have designated as desnutrin. The novel gene is predominantly expressed in adipose tissue and its expression is induced early during 3T3-L1 adipocyte differentiation. Desnutrin mRNA levels are regulated by the nutritional status of animals, being transiently induced during fasting. In vitro, desnutrin gene expression is up-regulated by dexamethasone in a dose dependent manner but not by cAMP, suggesting that glucocorticoids could mediate the increase in desnutrin mRNA levels observed during fasting. Desnutrin mRNA codes for a putative protein of 486 amino acids containing a patatin-like domain, characteristic of many plant acyl hydrolases belonging to the patatin family. Confocal microscopy of desnutrin-EGFP protein transfected cells shows that the fusion protein localizes in the cytoplasm. Moreover, cells overexpressing desnutrin by transfection show an increase in triglyceride hydrolysis. Interestingly, we also found that desnutrin gene expression level was lower in ob/ob and db/db obese mouse models. Overall, our data suggest that the newly identified desnutrin gene codes for an adipocyte protein that may function as a lipase and play a role in the adaptive response to low energy state, such as fasting, by providing fatty acids to other tissues for oxidation. In addition, decreased expression of desnutrin in obesity models suggests its possible contribution to pathophysiology of obesity.


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