Identification of Nesfatin-1 in Human and Murine Adipose Tissue: A Novel Depot-Specific Adipokine with Increased Levels in Obesity

• Published in: Endocrinology (Philadelphia) 2010-07, Vol.151 (7), p.3169-3180
• Main Authors: Ramanjaneya, Manjunath, Chen, Jing, Brown, James E, Tripathi, Gyanendra, Hallschmid, Manfred, Patel, Suketu, Kern, Werner, Hillhouse, Edward W, Lehnert, Hendrik, Tan, Bee K, Randeva, Harpal S
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes; Adipokines - genetics; Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Biological and medical sciences; Blotting, Western; Body fat; Body mass index; Body size; Calcium-Binding Proteins - genetics; Cell Differentiation - genetics; Cell Differentiation - physiology; Cells, Cultured; Communication; Culture media; Cytokines; Cytokines - pharmacology; Deprivation; Dexamethasone; Dexamethasone - pharmacology; Dietary Fats - pharmacology; Dietary restrictions; DNA-Binding Proteins - genetics; Energy balance; Enzyme-Linked Immunosorbent Assay; Explants; Food; Fundamental and applied biological sciences. Psychology; Gene expression; Homeostasis; Humans; Hypothalamus; Immunohistochemistry; In Vitro Techniques; Inflammation; Insulin; Insulin - pharmacology; Interleukin 6; Intracellular; Male; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; mRNA; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Obesity; Obesity - blood; Obesity - metabolism; Peptide Hormones - blood; Peptide Hormones - genetics; Peptide Hormones - metabolism; Preadipocytes; Protein expression; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tumor necrosis factor-α; Vertebrates: endocrinology; Western blotting
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2009-1358

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 (TNFα 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-α, 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. Nesfatin-1 is an anorexogenic adipokine predominantly produced by subcutaneous adipose tissue, levels of which are elevated in obesity and decreased with food deprivation.