Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis.
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.
Villena
Josep A
JA
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA.
Roy
Suheeta
S
Sarkadi-Nagy
Eszter
E
Kim
Kee-Hong
KH
Sul
Hei Sook
HS
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000502:physiology*; D002498:Centrifugation; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005938:Glucocorticoids / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006868:Hydrolysis; D008049:Lipase; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D013997:Time Factors; D014162:Transfection; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism; D015854:Up-Regulation; D000217:Acyltransferases
D002265:Carboxylic Ester Hydrolases; D018076:DNA, Complementary; D005938:Glucocorticoids; D049452:Green Fluorescent Proteins; D008049:Lipase; D010100:Oxygen; D010940:Plant Proteins; D012313:RNA; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014280:Triglycerides; C043222:patatin protein, Solanum tuberosum; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases