GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells

World J Gastroenterol. 2014 Nov 14;20(42):15727-35. doi: 10.3748/wjg.v20.i42.15727.

Abstract

Aim: To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2 cells.

Methods: The mRNA expression of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor-gamma 2 (PPAR-γ2), adiponectin, leptin, resistin, adiponectin receptor 1 (AdipoR1), adiponectin receptor 2 (AdipoR2), and the long isoform of leptin receptor (OB-Rb) and protein levels of adiponectin, leptin, and resistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay, respectively, on days 0, 2, 4, 6, and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064. Moreover, mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0, 12, 24, and 48 h in HepG2 cells treated with GW4064.

Results: The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, resistin, AdipoR1, AdipoR2, and OB-Rb and protein levels of adiponectin, leptin, and resistin increased along with differentiation of 3T3-L1 preadipocytes (P < 0.05 for all). The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, and AdipoR2 in 3T3-L1 preadipocytes, and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064, when compared with the control group (P < 0.05 for all). A similar trend was observed for protein levels of adipokines (including adiponectin, leptin and resistin). However, the expression of resistin, AdipoR1, and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064.

Conclusion: The FXR agonist through regulating, at least partially, the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.

Keywords: 3T3-L1 cells; Adipokine receptors; Adipokines; Farnesoid X receptor; HepG2 cells; Nonalcoholic fatty liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipokines / genetics
  • Adipokines / metabolism*
  • Animals
  • Hep G2 Cells
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Isoxazoles / pharmacology*
  • Mice
  • PPAR gamma / drug effects
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Adiponectin / drug effects
  • Receptors, Adiponectin / genetics
  • Receptors, Adiponectin / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Leptin / drug effects
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • Signal Transduction / drug effects
  • Time Factors
  • Up-Regulation

Substances

  • Adipokines
  • Isoxazoles
  • PPAR gamma
  • RNA, Messenger
  • Receptors, Adiponectin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Leptin
  • farnesoid X-activated receptor
  • GW 4064