Desnutrin, an Adipocyte Gene Encoding a Novel Patatin Domain-containing Protein, Is Induced by Fasting and Glucocorticoids

By J. Villena, Suheeta Roy, E. Sarkadi-Nagy, Kee-Hong Kim, H. Sul. Journal of Biological Chemistry, 2004

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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 expressed predominantly in adipose tissue, and its expression is induced early during 3T3-L1 adipocyte differentiation. Desnutrin mRNA levels were regulated by the nutritional status of animals, being transiently induced during fasting. In vitro desnutrin gene expression was 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 486-amino acid putative protein containing a patatin-like domain, characteristic of many plant acyl hydrolases belonging to the patatin family. Confocal microscopy of enhanced green fluorescent protein-tagged desnutrin protein-transfected cells showed that the fusion protein localized in the cytoplasm. Moreover, cells overexpressing desnutrin by transfection showed an increase in triglyceride hydrolysis. Interestingly, we also found that the 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 a 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 the pathophysiology of obesity.

Subfields: Biochemistry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/21e7b22c96bd8b7cd80fc3c496e2f4699b73e15b

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Citations in the corpus

Non Alcoholic Fatty Liver Disease, Hepatic Insulin Resistance and Type 2 Diabetes (2014, background): “This seemingly paradoxical effect could be explained by a specific compartmentation pattern of DAGs.”
Growth and Lipid Metabolism of the Pacific White Shrimp Litopenaeus vannamei at Different Salinities (2014, background): “…mobilization has increased, because ATGL (TAG hydrolysis), LPL, and HSL are crucial enzymes in lipid mobilization by performing the first step in hydrolyzing TAG to generate diacylglycerol and free fatty acid (Osuga et al. 2000, Jenkins et al. 2004, Villena et al. 2004, Zimmermann et al. 2004).”
Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores (2011, background): “Virtually all tissues examined express measurable amounts of ATGL mRNA [10,31,44,45].”
FAT SIGNALS - Lipases and Lipolysis in Lipid Metabolism and Signaling (2012, background): “The enzyme, first described in 2004 (Jenkins et al., 2004; Villena et al., 2004; Zimmermann et al., 2004), belongs to the family patatin domain-containing proteins including nine human and eight murine members.”
Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. (2006, background): “Several previous studies have provided experimental evidence for a defect in TG hydrolysis or the recycling of acylglycerides to glycerophospholipids in fibroblasts of CDS patients (Igal and Coleman, 1996; Igal and Coleman, 1998; Williams et al., 1991).”
Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila. (2005, background): “Accordingly, additional TAG lipases of the nutrin family (Villena et al., 2004), such as the most recently identified human adipose triglyceride lipase (ATGL) (Zimmermann et al., 2004), have been implicated in mammalian lipolysis.”
11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. (2013, background): “With these caveats, glucocorticoids alone stimulate fatty acid uptake via lipoprotein lipase and lipolysis via induction of hormone-sensitive lipase and adipose triglyceride lipase (643, 730) and thus promote free fatty acid synthesis which increases metabolic fuel provision.”