Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity

Manjunath Ramanjaneya, Jing Chen, James Brown, Gyanendra Tripathi, Manfred Hallschmid, Suketu Patel, Werner Kern, Edward W. Hillhouse, Hendrik Lehnert, Bee K. Tan, Harpal S. Randeva

Research output: Contribution to journalArticle

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 (TNFa 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-a, 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.
LanguageEnglish
Pages3169-3180
Number of pages12
JournalEndocrinology
Volume151
Issue number7
Early online date28 Apr 2010
DOIs
Publication statusPublished - 1 Jul 2010

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Adipokines
Adipose Tissue
Food Deprivation
Obesity
Dexamethasone
Insulin
Interleukin-6
Fats
Cytokines
Proteins
Protein Precursors
Nonesterified Fatty Acids
Adipocytes
Hypothalamus
Culture Media
Body Mass Index
Homeostasis
Western Blotting
Maintenance
Gene Expression

Cite this

Ramanjaneya, Manjunath ; Chen, Jing ; Brown, James ; Tripathi, Gyanendra ; Hallschmid, Manfred ; Patel, Suketu ; Kern, Werner ; Hillhouse, Edward W. ; Lehnert, Hendrik ; Tan, Bee K. ; Randeva, Harpal S. / Identification of nesfatin-1 in human and murine adipose tissue : a novel depot-specific adipokine with increased levels in obesity. In: Endocrinology. 2010 ; Vol. 151, No. 7. pp. 3169-3180.
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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 (TNFa 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-a, 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.",
author = "Manjunath Ramanjaneya and Jing Chen and James Brown and Gyanendra Tripathi and Manfred Hallschmid and Suketu Patel and Werner Kern and Hillhouse, {Edward W.} and Hendrik Lehnert and Tan, {Bee K.} and Randeva, {Harpal S.}",
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Ramanjaneya, M, Chen, J, Brown, J, Tripathi, G, Hallschmid, M, Patel, S, Kern, W, Hillhouse, EW, Lehnert, H, Tan, BK & Randeva, HS 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. https://doi.org/10.1210/en.2009-1358

Identification of nesfatin-1 in human and murine adipose tissue : a novel depot-specific adipokine with increased levels in obesity. / Ramanjaneya, Manjunath; Chen, Jing; Brown, James; Tripathi, Gyanendra; Hallschmid, Manfred; Patel, Suketu; Kern, Werner; Hillhouse, Edward W.; Lehnert, Hendrik; Tan, Bee K.; Randeva, Harpal S.

In: Endocrinology, Vol. 151, No. 7, 01.07.2010, p. 3169-3180.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of nesfatin-1 in human and murine adipose tissue

T2 - Endocrinology

AU - Ramanjaneya, Manjunath

AU - Chen, Jing

AU - Brown, James

AU - Tripathi, Gyanendra

AU - Hallschmid, Manfred

AU - Patel, Suketu

AU - Kern, Werner

AU - Hillhouse, Edward W.

AU - Lehnert, Hendrik

AU - Tan, Bee K.

AU - Randeva, Harpal S.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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 (TNFa 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-a, 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.

AB - 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 (TNFa 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-a, 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.

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