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Article

T-Cadherin Finetunes Proliferation–Differentiation During Adipogenesis via PI3K–AKT Signaling Pathway

1
Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia
2
Institute of Experimental Cardiology, National Medical Research Center of Cardiology Named after Academician E.I. Chazov, 121552 Moscow, Russia
3
Center for Regenerative Medicine, Medical Research and Education Institute, Lomonosov Moscow State University, 119192 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(19), 9646; https://doi.org/10.3390/ijms26199646
Submission received: 27 August 2025 / Revised: 23 September 2025 / Accepted: 30 September 2025 / Published: 2 October 2025

Abstract

Adipose tissue renewal requires precise coordination of stem/progenitor cell proliferation, preadipocyte commitment, and terminal adipocyte differentiation. T-cadherin (CDH13), an atypical GPI-anchored cadherin, is expressed in adipose tissue and functions as a receptor for high-molecular-weight (HMW) adiponectin—a key adipokine produced by adipose tissue and involved in metabolic regulation. While T-cadherin is implicated in cardiovascular and metabolic homeostasis, its role in adipogenesis still remains poorly understood. In this study, we used the 3T3-L1 preadipocyte model to investigate the function of T-cadherin in adipocyte differentiation. We analyzed T-cadherin expression dynamics during differentiation and assessed how T-cadherin overexpression or knockdown affects lipid accumulation, expression of adipogenic markers, and key signaling pathways including ERK, PI3K–AKT, AMPK, and mTOR. Our findings demonstrate that T-cadherin acts as a negative regulator of adipogenesis. T-cadherin overexpression ensured a proliferative, undifferentiated cell state, delaying early adipogenic differentiation and suppressing both lipid droplet accumulation and the expression of adipogenic markers. In contrast, T-cadherin downregulation accelerated differentiation, enhanced lipid accumulation, and increased insulin responsiveness, as indicated by PI3K–AKT pathway activation at specific stages of adipogenesis. These results position T-cadherin as a key modulator of adipose tissue plasticity, regulating the balance between progenitor expansion and terminal differentiation, with potential relevance to obesity and metabolic disease.
Keywords: T-cadherin; CDH13; adiponectin; adipogenesis; 3T3-L1; insulin signaling T-cadherin; CDH13; adiponectin; adipogenesis; 3T3-L1; insulin signaling

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MDPI and ACS Style

Klimovich, P.; Brodsky, I.; Dzreyan, V.; Ivleva, M.; Grigorieva, O.; Meshcheriakov, M.; Semina, E.; Sysoeva, V.; Tkachuk, V.; Rubina, K. T-Cadherin Finetunes Proliferation–Differentiation During Adipogenesis via PI3K–AKT Signaling Pathway. Int. J. Mol. Sci. 2025, 26, 9646. https://doi.org/10.3390/ijms26199646

AMA Style

Klimovich P, Brodsky I, Dzreyan V, Ivleva M, Grigorieva O, Meshcheriakov M, Semina E, Sysoeva V, Tkachuk V, Rubina K. T-Cadherin Finetunes Proliferation–Differentiation During Adipogenesis via PI3K–AKT Signaling Pathway. International Journal of Molecular Sciences. 2025; 26(19):9646. https://doi.org/10.3390/ijms26199646

Chicago/Turabian Style

Klimovich, Polina, Ilya Brodsky, Valentina Dzreyan, Marianna Ivleva, Olga Grigorieva, Mark Meshcheriakov, Ekaterina Semina, Veronika Sysoeva, Vsevolod Tkachuk, and Kseniya Rubina. 2025. "T-Cadherin Finetunes Proliferation–Differentiation During Adipogenesis via PI3K–AKT Signaling Pathway" International Journal of Molecular Sciences 26, no. 19: 9646. https://doi.org/10.3390/ijms26199646

APA Style

Klimovich, P., Brodsky, I., Dzreyan, V., Ivleva, M., Grigorieva, O., Meshcheriakov, M., Semina, E., Sysoeva, V., Tkachuk, V., & Rubina, K. (2025). T-Cadherin Finetunes Proliferation–Differentiation During Adipogenesis via PI3K–AKT Signaling Pathway. International Journal of Molecular Sciences, 26(19), 9646. https://doi.org/10.3390/ijms26199646

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