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.
References
[1]
WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894: i–xii, 1–253.
[2]
Billington CJ, Epstein LH, Goodwin NJ, Hill JO, Pi-Sunyer JX, et al. (2000) Overweight, obesity, and health risk. National Task Force on the Prevention and Treatment of Obesity. Arch Intern Med 160: 898–904.
[3]
Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, et al. (2006) Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295: 1549–1555.
[4]
Luo J, Hu FB (2002) Time trends of obesity in pre-school children in China from 1989 to 1997. Int J Obes Relat Metab Disord 26: 553–558.
[5]
Rennie KL, Jebb SA (2005) Prevalence of obesity in Great Britain. Obes Rev 6: 11–12.
[6]
Wang Y, Monteiro C, Popkin BM (2002) Trends of obesity and underweight in older children and adolescents in the United States, Brazil, China, and Russia. Am J Clin Nutr 75: 971–977.
[7]
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425–432.
[8]
Spiegelman BM, Flier JS (2001) Obesity and the regulation of energy balance. Cell 104: 531–543.
Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404: 661–671.
[11]
Barsh GS, Farooqi IS, O’Rahilly S (2000) Genetics of body-weight regulation. Nature 404: 644–651.
[12]
Rosen ED, Spiegelman BM (2000) Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 16: 145–171.
[13]
Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. Journal of Clinical Endocrinology & Metabolism 89: 2548–2556.
[14]
Ahima RS, Flier JS (2000) Adipose tissue as an endocrine organ. Trends in Endocrinology and Metabolism 11: 327–332.
[15]
Mohamed-Ali V, Pinkney JH, Coppack SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity 22: 1145–1158.
[16]
Trayhurn P, Beattie JH (2001) Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proceedings of the Nutrition Society 60: 329–339.
[17]
Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA (2001) The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. American Journal of Physiology-Endocrinology and Metabolism 280: E827–E847.
[18]
Flier JS (1995) The Adipocyte - Storage Depot or Node on the Energy Information Superhighway. Cell 80: 15–18.
[19]
Kennedy AR, Pissios P, Otu H, Xue BZ, Asakura K, et al. (2007) A high-fat, ketogenic diet induces a unique metabolic state in mice. American Journal of Physiology-Endocrinology and Metabolism 292: E1724–E1739.
[20]
Xu HY, Barnes GT, Yang Q, Tan Q, Yang DS, et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation 112: 1821–1830.
[21]
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, et al. (2003) Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation 112: 1796–1808.
Vilella AJ, Severin J, Ureta-Vidal A, Heng L, Durbin R, et al. (2009) EnsemblCompara GeneTrees: Complete, duplication-aware phylogenetic trees in vertebrates. Genome Research 19: 327–335.
[24]
Boratyn GM, Schaffer AA, Agarwala R, Altschul SF, Lipman DJ, et al. (2012) Domain enhanced lookup time accelerated BLAST. Biol Direct 7: 12.
[25]
UniProtConsortium (2012) Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res 40: D71–75.
[26]
Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, et al. (2003) The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: A bioinformatics assessment (vol 13, pg 2265, 2003). Genome Research 13: 2759–2759.
[27]
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, et al. (2009) Identification and Importance of Brown Adipose Tissue in Adult Humans. New England Journal of Medicine 360: 1509–1517.
[28]
Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, et al. (2009) Functional Brown Adipose Tissue in Healthy Adults (vol 360, pg 1518, 2009). New England Journal of Medicine 361: 1123–1123.
[29]
Guberman JM, Ai J, Arnaiz O, Baran J, Blake A, et al. (2011) BioMart Central Portal: an open database network for the biological community. Database (Oxford) 2011: bar041.
