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Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity
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Ramanjaneya, Manjunath, Chen, Jing, Brown, James E. P., Tripathi, G. (Gyanendra), Hallschmid, Manfred, Patel, Suketu, Kern, Werner, Hillhouse, Edward W., Lehnert, Hendrik, Tan, Bee K. and Randeva, Harpal S.. (2010) Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity. Endocrinology, Vol.151 (No.7). pp. 3169-3180. ISSN 0013-7227
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Official URL: http://dx.doi.org/10.1210/en.2009-1358
Abstract
Nesfatin-1 is a recently identified anorexigenic peptide derived from its precursor protein, non-esterified fatty acid/nucleobindin 2 (NUCB2). Although the hypothalamus is pivotal for the maintenance of energy homeostasis, adipose tissue plays an important role in the integration of metabolic activity and energy balance by communicating with peripheral organs and the brain via adipokines. Currently no data exist on nesfatin-1 expression, regulation, and secretion in adipose tissue. We therefore investigated NUCB2/nesfatin-1 gene and protein expression in human and murine adipose tissue depots. Additionally, the effects of insulin, dexamethasone, and inflammatory cytokines and the impact of food deprivation and obesity on nesfatin-1 expression were studied by quantitative RT-PCR and Western blotting. We present data showing NUCB2 mRNA(P < 0.001), nesfatin-1 intracellular protein (P < 0.001), and secretion (P < 0.01) were significantly higher in sc adipose tissue compared with other depots. Also, nesfatin-1 protein expression was significantly increased in high-fat-fed mice (P < 0.01) and reduced under food deprivation (P < 0.01) compared with controls. Stimulation of sc adipose tissue explants with inflammatory cytokines (TNF alpha and IL-6), insulin, and dexamethasone resulted in a marked increase in intracellular nesfatin-1 levels. Furthermore, we present evidence that the secretion of nesfatin-1 into the culture media was dramatically increased during the differentiation of 3T3-L1 preadipocytes into adipocytes (P < 0.001) and after treatments with TNF-alpha, IL-6, insulin, and dexamethasone (P < 0.01). In addition, circulating nesfatin-1 levels were higher in high-fat-fed mice (P < 0.05) and showed positive correlation with body mass index in human. We report that nesfatin-1 is a novel depot specific adipokine preferentially produced by sc tissue, with obesity-and food deprivation-regulated expression. (Endocrinology 151: 3169-3180, 2010)
| Item Type: | Journal Article |
|---|---|
| Subjects: | R Medicine > RC Internal medicine |
| Divisions: | Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School |
| Journal or Publication Title: | Endocrinology |
| Publisher: | The Endocrine Society |
| ISSN: | 0013-7227 |
| Date: | July 2010 |
| Volume: | Vol.151 |
| Number: | No.7 |
| Number of Pages: | 12 |
| Page Range: | pp. 3169-3180 |
| Identification Number: | 10.1210/en.2009-1358 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | General Charities of the City of Coventry, Wellcome Trust, United Kingdom |
| URI: | http://wrap.warwick.ac.uk/id/eprint/5660 |
Data sourced from Thomson Reuters' Web of Knowledge
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