Nrac, a Novel Nutritionally-Regulated Adipose and Cardiac-Enriched Gene

Obesity increases the risk of multiple diseases, such as type 2 diabetes and coronary heart diseases, and therefore the current obesity epidemic poses a major public health issue. Therapeutic approaches are urgently needed to treat obesity as well as its complications. Plasma-membrane proteins with restricted tissue distributions are attractive drug targets, because of their accessibility to various drug delivery mechanisms and potentially alleviated side effects. To identify genes involved in metabolism, we performed RNA-Seq on fat in mice treated with a high-fat diet or fasting. Here we show that the gene A530016L24Rik (human ortholog C14orf180), named Nrac, is a novel nutritionally-regulated adipose and cardiac-enriched gene. Nrac is expressed specifically and abundantly in fat and the heart. Both fasting and obesity reduced Nrac expression in white adipose tissue, and fasting reduced its expression in brown fat. Nrac is localized to the plasma membrane, and highly induced during adipocyte differentiation. Nrac is therefore a novel adipocyte marker and has potential functions in metabolism.

[1]  Thomas L. Madden,et al.  Domain enhanced lookup time accelerated BLAST , 2012, Biology Direct.

[2]  J. Silberg,et al.  A transposase strategy for creating libraries of circularly permuted proteins , 2012, Nucleic acids research.

[3]  B. Spiegelman,et al.  Identifying novel transcriptional components controlling energy metabolism. , 2011, Cell metabolism.

[4]  The UniProt Consortium,et al.  Reorganizing the protein space at the Universal Protein Resource (UniProt) , 2011, Nucleic Acids Res..

[5]  Damian Smedley,et al.  BioMart Central Portal: an open database network for the biological community , 2011, Database J. Biol. Databases Curation.

[6]  G. Steinberg,et al.  Adipose tissue as an endocrine organ , 2010, Molecular and Cellular Endocrinology.

[7]  J. Orava,et al.  Functional brown adipose tissue in healthy adults. , 2009, The New England journal of medicine.

[8]  E. Palmer,et al.  Identification and importance of brown adipose tissue in adult humans. , 2009, The New England journal of medicine.

[9]  H. Otu,et al.  A high-fat, ketogenic diet induces a unique metabolic state in mice. , 2007, American journal of physiology. Endocrinology and metabolism.

[10]  K. Flegal,et al.  Prevalence of overweight and obesity in the United States, 1999-2004. , 2006, JAMA.

[11]  S. Jebb,et al.  Prevalence of obesity in Great Britain , 2005, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[12]  J. Flier,et al.  Adipose Tissue as an Endocrine Organ , 2014 .

[13]  J. Flier.  Obesity Wars Molecular Progress Confronts an Expanding Epidemic , 2004, Cell.

[14]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[15]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[16]  Somasekar Seshagiri,et al.  The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. , 2003, Genome research.

[17]  B. Popkin,et al.  Trends of obesity and underweight in older children and adolescents in the United States, Brazil, China, and Russia. , 2002, The American journal of clinical nutrition.

[18]  F. Hu,et al.  Time trends of obesity in pre-school children in China from 1989 to 1997 , 2002, International Journal of Obesity.

[19]  J. Beattie,et al.  Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ , 2001, Proceedings of the Nutrition Society.

[20]  G. Frühbeck,et al.  The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. , 2001, American journal of physiology. Endocrinology and metabolism.

[21]  Bruce M. Spiegelman,et al.  Obesity and the Regulation of Energy Balance , 2001, Cell.

[22]  A. Astrup,et al.  Obesity : Preventing and managing the global epidemic , 2000 .

[23]  Gregory S. Barsh,et al.  Genetics of body-weight regulation , 2000, Nature.

[24]  S. Woods,et al.  Central nervous system control of food intake , 2000, Nature.

[25]  S. Coppack,et al.  Adipose tissue as an endocrine and paracrine organ , 1998, International Journal of Obesity.

[26]  J. Flier,et al.  The adipocyte: Storage depot or node on the energy information superhighway? , 1995, Cell.

[27]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[28]  Albert J. Vilella,et al.  EnsemblCompara GeneTrees: Complete, duplication-aware phylogenetic trees in vertebrates. , 2009, Genome research.

[29]  B. Spiegelman,et al.  Molecular regulation of adipogenesis. , 2000, Annual review of cell and developmental biology.

[30]  Leonard H. Epstein,et al.  Overweight, obesity, and health risk. , 2000, Archives of internal medicine.

[31]  Who Consultation on Obesity.  Obesity: preventing and managing the global epidemic. Report of a WHO consultation. , 2000, World Health Organization technical report series.

[32]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.