Skip to main content
Article thumbnail
Location of Repository

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

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


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

Topics: QL, QP
Publisher: Endocrine Society
Year: 2009
OAI identifier:

Suggested articles


  1. (2001). A new mathematical model for relative quantification in real-time RT-PCR. doi
  2. (2004). Adipose tissue as an endocrine organ. doi
  3. (2001). Culture of adipose tissue and isolated adipocytes. doi
  4. (1997). Diet-induced obese mice develop peripheral, but not central, resistance to leptin.
  5. (2006). Fru ¨hbeck G
  6. HanDC,IsonoM,ChenS,CasarettoA,HongSW,WolfG,ZiyadehFN2001 Leptin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF- type II receptor expression. doi
  7. Hansen-AlgenstaedtN,BeilFU,AlgenstaedtP2007TNF-altersvisfatinand adiponectin levels in human fat. doi
  8. (2006). Increase in visfatin after weight loss induced by gastroplastic surgery. doi
  9. (2005). Induction of leptin receptor expression in the liver by leptin and food deprivation.
  10. KapiotisS,WolztM2006Theadipokinevisfatinismarkedlyelevatedinobese children.
  11. (1997). Leptin activates PI-3 kinase in C2C12 myotubes via janus kinase-2 (JAK-2) and insulin receptor substrate-2 (IRS-2) dependent pathways. doi
  12. (2002). Leptin and soluble leptin receptor levels in obese and weight-losing individuals. doi
  13. (1999). Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. doi
  14. (2004). Modulation of direct leptin signaling by soluble leptin receptor. doi
  15. MurakamiT,YamashitaT,IidaM,KuwajimaM,ShimaK1997Ashortform of leptin receptor performs signal transduction.
  16. (2004). Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin. doi
  17. (2006). Reduced plasma visfatin/pre-B cell colonyenhancingfactorinobesityisnotrelatedtoinsulinresistanceinhumans.JClin Endocrinol Metab 91:3165–3170 doi
  18. (1996). Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss. doi
  19. SandeepS,VelmuruganK,DeepaR,MohanV2007Serumvisfatininrelation to visceral fat, obesity, and type 2 diabetes mellitus in Asian Indians.
  20. Taylor PR2007Bodymassindex,percentbodyfat,andregionalbodyfatdistribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study.
  21. (2005). Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.