In vivo and ex vivo regulation of visfatin production by leptin in human and murine adipose tissue: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways

Bee K. Tan, Jing Chen, Raghu Adya, Manjunath Ramanjaneya, Vinod Menon, Clifford J. Bailey, James Brown, Hendrik Lehnert, Harpal S. Randeva

Research output: Contribution to journalArticle

Abstract

Visfatin is an adipogenic adipokine with increased levels in obesity, properties common to leptin. Thus, leptin may modulate visfatin production in adipose tissue (AT). Therefore, we investigated the effects of leptin on visfatin levels in 3T3-L1 adipocytes and human/murine AT, with or without a leptin antagonist. The potential signaling pathways and mechanisms regulating visfatin production in AT was also studied. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. ELISA was performed to measure visfatin levels in conditioned media of AT explants, and small interfering RNA technology was used to reduce leptin receptor expression. Leptin significantly (P<0.01) increased visfatin levels in human and murine AT with a maximal response at leptin 10(-9) M, returning to baseline at leptin 10(-7) M. Importantly, ip leptin administration to C57BL/6 ob/ob mice further supported leptin-induced visfatin protein production in omental AT (P<0.05). Additionally, soluble leptin receptor levels rose with concentration dependency to a maximal response at leptin 10(-7) M (P<0.01). The use of a leptin antagonist negated the induction of visfatin and soluble leptin receptor by leptin. Furthermore, leptin-induced visfatin production was significantly decreased in the presence of MAPK and phosphatidylinositol 3-kinase inhibitors. Also, when the leptin eceptor gene was knocked down using small interfering RNA, eptin-induced visfatin expression was significantly decreased. Thus, leptin increases visfatin production in AT in vivo and ex vivo via pathways involving MAPK and phosphatidylinositol 3-kinase signaling. The pleiotropic effects of leptin may be partially mediated by visfatin.
LanguageEnglish
Pages3530-3539
Number of pages10
JournalEndocrinology
Volume150
Issue number8
DOIs
Publication statusPublished - Aug 2009

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Nicotinamide Phosphoribosyltransferase
Phosphatidylinositol 3-Kinase
Leptin
Mitogen-Activated Protein Kinases
Adipose Tissue
Leptin Receptors
Small Interfering RNA
Adipokines

Bibliographical note

Copyright © 2009 by The Endocrine Society

Keywords

  • visfatin
  • adipogenic adipokine
  • obesity
  • leptin

Cite this

Tan, Bee K. ; Chen, Jing ; Adya, Raghu ; Ramanjaneya, Manjunath ; Menon, Vinod ; Bailey, Clifford J. ; Brown, James ; Lehnert, Hendrik ; Randeva, Harpal S. / In vivo and ex vivo regulation of visfatin production by leptin in human and murine adipose tissue: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. In: Endocrinology. 2009 ; Vol. 150, No. 8. pp. 3530-3539.
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In vivo and ex vivo regulation of visfatin production by leptin in human and murine adipose tissue: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. / Tan, Bee K.; Chen, Jing; Adya, Raghu; Ramanjaneya, Manjunath; Menon, Vinod; Bailey, Clifford J.; Brown, James; Lehnert, Hendrik; Randeva, Harpal S.

In: Endocrinology, Vol. 150, No. 8, 08.2009, p. 3530-3539.

Research output: Contribution to journalArticle

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AU - Tan, Bee K.

AU - Chen, Jing

AU - Adya, Raghu

AU - Ramanjaneya, Manjunath

AU - Menon, Vinod

AU - Bailey, Clifford J.

AU - Brown, James

AU - Lehnert, Hendrik

AU - Randeva, Harpal S.

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