Wnt/β-Catenin Signaling in Adipose Tissue Differentiation

The canonical Wnt/β-catenin pathway is a pivotal regulator of adipocyte lineage determination and maturation. In the absence of Wnt ligands, β-catenin is phosphorylated and targeted for proteasomal degradation. Upon Wnt binding to Frizzled and LRP5/6 co-receptors, β-catenin stabilises and translocates to the nucleus, where it associates with T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors to modulate gene expression. Active signalling maintains mesenchymal progenitors and preadipocytes in an undifferentiated, proliferative state, blocking induction of key adipogenic transcription factors such as PPARγ and C/EBPα. Temporal suppression of Wnt activity is therefore required for initiation of adipogenesis, whereas sustained pathway engagement can bias progenitors towards osteoblastic fates or impair beige/brown fat thermogenic programmes. Emerging evidence highlights context-dependent modulation by secreted agonists (RSPOs) and antagonists (DKKs, sFRPs), enabling fine-tuning of depot-specific adipose development, energy storage and metabolic homeostasis.

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Wnt/β-Catenin Signaling in Adipose Tissue Differentiation publication trend

The graph below shows the total number of articles in wnt/β-catenin signaling in adipose tissue differentiation across all publications each year (not limited to Nature Index journals).

Technical terms

Wnt ligands: A family of secreted glycoproteins that initiate canonical signalling through Frizzled receptors and LRP5/6 co-receptors.

β-Catenin: A central effector protein stabilised upon Wnt activation, which translocates to the nucleus to regulate target gene transcription.

Preadipocyte: A proliferative adipocyte precursor cell that requires Wnt suppression to enter terminal differentiation into mature adipocytes.

RSPO1 (R-spondin 1): A secreted enhancer of Wnt signalling that potentiates ligand–receptor interactions, influencing adipocyte thermogenesis and expansion.

Thermogenesis: The process by which brown or beige adipocytes generate heat via mitochondrial uncoupling proteins, critical for energy expenditure.

Dedifferentiation: The reversal of a differentiated adipocyte to a more progenitor-like state, often mediated by stress-activated Wnt/β-catenin signalling.

References

1. Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet‐Induced Adiposity. Advanced Science (2023).
2. Hypertonicity induces mitochondrial extracellular vesicles (MEVs) that activate TNF-α and β-catenin signaling to promote adipocyte dedifferentiation. Stem Cell Research & Therapy (2023).