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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

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Tan, Bee K., Chen, Jing, Brown, James, Adya, Raghu, Ramanjaneya, Manjunath, Menon, Vinod, Bailey, C. J. (Clifford J.), Lehnert, Hendrik and Randeva, Harpal S.. (2009) 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. Endocrinology, Vol.15 (No.8). pp. 3530-3539. ISSN 0013-7227

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Official URL: http://dx.doi.org/10.1210/en.2008-1655

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 receptor gene was knocked down using small interfering RNA, leptin-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.

Item Type:	Journal Article
Subjects:	Q Science > QL Zoology Q Science > QP Physiology
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
Library of Congress Subject Headings (LCSH):	Adipose tissues -- Research, Enzymes -- Regulation, Leptin -- Research, Obesity -- Genetic aspects, Endocrinology, Comparative -- Great Britain, Mice -- Endocrinology -- Research, Endocrinology -- Research
Journal or Publication Title:	Endocrinology
Publisher:	Endocrine Society
ISSN:	0013-7227
Date:	August 2009
Volume:	Vol.15
Number:	No.8
Page Range:	pp. 3530-3539
Identification Number:	10.1210/en.2008-1655
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	General Charities of the City of Coventry (GCCC)
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URI:	http://wrap.warwick.ac.uk/id/eprint/2256