title: Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity.
abstract: Nesfatin-1 is a recently identified anorexigenic peptide derived from its precursor protein, nonesterified 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 (TNFalpha 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.
authors.affiliation: Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Ramanjaneya
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: James E
authors.initials: JE
authors.lastname: Brown
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Tripathi
authors.forename: Manfred
authors.initials: M
authors.lastname: Hallschmid
authors.forename: Suketu
authors.initials: S
authors.lastname: Patel
authors.forename: Werner
authors.initials: W
authors.lastname: Kern
authors.forename: Edward W
authors.initials: EW
authors.lastname: Hillhouse
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D041721:3T3-L1 Cells; D054392:Adipokines / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000080866:Nucleobindins; D009765:Obesity / Q000097:blood / Q000378:metabolism; D036361:Peptide Hormones / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054392:Adipokines; D002135:Calcium-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D007328:Insulin; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D036361:Peptide Hormones; D003907:Dexamethasone