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Updated: Aug 15, 2025

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

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Early adipogenesis is repressed through the newly identified FHL2-NFAT5 signaling complex

Maria P Clemente-Olivo1, Miguel Hernández-Quiles2, Rinske Sparrius3

  • 1Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, and Amsterdam Gastroenterology, Endocrinology and Metabolism, University of Amsterdam, Amsterdam, the Netherlands.

Cellular Signalling
|January 7, 2023
PubMed

Insights

The LIM-homeodomain protein FHL2 inhibits adipocyte differentiation by interacting with NFAT5. Downregulation of FHL2 is crucial for early adipogenesis, and its increased expression with aging may impair stem cell differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The LIM-domain-only protein FHL2 influences mesenchymal stem cell differentiation into osteoblast and myocyte lineages.
  • Its role in adipocyte differentiation, particularly in the context of aging, remains largely unexplored.

Purpose of the Study:

  • To investigate the role of FHL2 in adipocyte differentiation.
  • To identify FHL2-interacting proteins involved in regulating adipogenesis.
  • To elucidate the mechanism by which FHL2 affects adipocyte lineage induction.

Main Methods:

  • Utilized mouse pre-adipocytes and the 3T3-L1 cell line.
  • Performed FHL2 gain-of-function and knockdown experiments.
  • Conducted RNA sequencing (RNAseq) for gene expression analysis and Oil-Red O (ORO) staining for lipid accumulation.
  • Employed affinity-purification mass spectrometry (AP-MS) to identify FHL2-interacting proteins.

Main Results:

  • FHL2 is expressed in pre-adipocytes and must be downregulated for accurate adipocyte differentiation.
  • Constitutive FHL2 overexpression significantly inhibits adipocyte differentiation in 3T3-L1 cells, suppressing the adipogenic gene program and lipid accumulation.
  • FHL2 interacts with Nuclear factor of activated T-cells 5 (NFAT5), an adipogenic inhibitor; this interaction is critical for FHL2's repressive effect.

Conclusions:

  • FHL2 acts as a novel inhibitor of early adipocyte differentiation.
  • The inhibitory function of FHL2 on adipogenesis is dependent on its interaction with NFAT5.
  • Increased FHL2 expression with aging may negatively impact mesenchymal stem cell differentiation, specifically inhibiting adipocyte development.
Keywords:
AdipogenesisAgingFHL2Mesenchymal stem cellNFAT5

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