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Updated: Jul 19, 2026

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
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Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis

Published on: April 1, 2022

Molecular determinants of FGF-21 activity-synergy and cross-talk with PPARgamma signaling

Julie S Moyers1, Tatiyana L Shiyanova, Farrokh Mehrbod

  • 1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.

Journal of Cellular Physiology
|October 26, 2006
PubMed

Insights

Fibroblast growth factor (FGF)-21 and peroxisome proliferator-activated receptor gamma (PPARgamma) synergize to enhance glucose transport in adipocytes. This study defines novel mechanisms for FGF-21 in glucose homeostasis.

Area of Science:

  • Metabolic research
  • Cell signaling
  • Diabetes research

Background:

  • Fibroblast growth factor (FGF)-21 regulates glucose transport independently of insulin.
  • FGF-21 demonstrates glucose and triglyceride-lowering effects in diabetic rodent models.
  • The precise metabolic regulatory mechanisms of FGF-21 require further elucidation.

Purpose of the Study:

  • To investigate the early signaling events triggered by FGF-21 in 3T3-L1 adipocytes.
  • To explore the interplay between FGF-21 and peroxisome proliferator-activated receptor gamma (PPARgamma) pathways.
  • To elucidate the synergistic effects on glucose transport.

Main Methods:

  • Treatment of 3T3-L1 adipocytes with FGF-21.
  • Analysis of intracellular calcium accumulation and protein phosphorylation (Akt, GSK-3, p70(S6K), SHP-2, MEK1/2, Stat3).
  • Assessment of PPARgamma protein expression and GLUT1 glucose transporter levels following chronic treatment and combination therapy with rosiglitazone.

Main Results:

  • FGF-21 treatment induced rapid intracellular calcium accumulation and phosphorylation of key signaling proteins.
  • Continuous FGF-21 exposure elevated PPARgamma protein expression.
  • Combined FGF-21 and rosiglitazone treatment synergistically increased GLUT1 expression and glucose transport.

Conclusions:

  • A novel synergy exists between FGF-21 and PPARgamma pathways in regulating glucose homeostasis.
  • FGF-21's mechanism of action involves interplay with PPARgamma signaling.
  • These findings offer new insights into FGF-21's role in metabolic regulation and potential therapeutic strategies for diabetes.

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