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Updated: Jun 17, 2026
07:09
Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System
Published on: May 10, 2020
PGC-1alpha negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erb(alpha) axis
Jennifer L Estall1, Jorge L Ruas, Cheol Soo Choi
1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Summary
Reduced PGC-1alpha in obese mice boosts FGF21, improving insulin sensitivity and lipid metabolism. This highlights PGC-1alpha
Area of Science:
- Metabolic regulation
- Hormonal signaling
- Hepatic function
Background:
- Fibroblast Growth Factor 21 (FGF21) is a key metabolic hormone.
- Obesity is linked to impaired insulin sensitivity and lipid metabolism.
Purpose of the Study:
- To investigate the role of PGC-1alpha in regulating FGF21.
- To elucidate the molecular mechanisms linking PGC-1alpha to FGF21 expression and metabolic improvements.
Main Methods:
- Utilized genetically modified obese mice with reduced PGC-1alpha levels.
- Conducted gain- and loss-of-function studies in primary mouse hepatocytes.
- Analyzed the involvement of Rev-Erbalpha, ALAS-1, and intracellular heme levels.
Main Results:
- Reduced hepatic PGC-1alpha expression increased FGF21 levels and improved insulin sensitivity.
- PGC-1alpha regulates hepatic FGF21 expression via Rev-Erbalpha and ALAS-1-mediated heme synthesis.
- Modulating intracellular heme levels mimicked PGC-1alpha effects on FGF21.
Conclusions:
- PGC-1alpha influences hepatic and systemic metabolism by controlling nuclear receptor ligand levels.
- The PGC-1alpha-heme-Rev-Erbalpha axis is a critical regulator of FGF21.
- Targeting this pathway may offer therapeutic strategies for metabolic disorders.
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