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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1645587

Targeting adipocyte differentiation with CRT0066101: Activation of AMPK signaling in 3T3-L1 cells

Provisionally accepted
Jinque  LuoJinque Luo1*Ling  WangLing Wang1Li  ZhangLi Zhang1Wenyu  TangWenyu Tang1Meijing  DengMeijing Deng2Yuxin  ShiYuxin Shi1Kun  XuKun Xu1Qingjun  WuQingjun Wu1Jieyang  ZhaoJieyang Zhao1Jinghuan  ZhangJinghuan Zhang1Xin  LiXin Li1
  • 1College of Pharmacy, Changsha Medical University, Changsha, China
  • 2Hunan Normal University, Changsha, China

The final, formatted version of the article will be published soon.

Obesity is marked by excessive fat accumulation resulting from adipocyte hypertrophy and hyperplasia, with adipocyte differentiation playing a central role.In this study, we examined the effects of CRT0066101 (CRT), a pan-PKD inhibitor, on adipocyte differentiation in 3T3-L1 cells. CRT significantly inhibited early-stage adipocyte differentiation, reduced lipid accumulation, and downregulated key adipogenic transcription factors, including PPARγ and C/EBPα. Mechanistically, CRT activated the AMPK pathway, a known negative regulator of adipocyte differentiation. Network pharmacology analysis further supported the involvement of AMPK in CRT's anti-adipogenic action. These findings identify CRT as a novel modulator of adipocyte differentiation through AMPK activation and highlight its potential as a therapeutic candidate for obesity and metabolic syndrome.

Keywords: Obesity, Adipocyte differentiation, CRT0066101, 3T3-L1, AMPK

Received: 12 Jun 2025; Accepted: 05 Aug 2025.

Copyright: © 2025 Luo, Wang, Zhang, Tang, Deng, Shi, Xu, Wu, Zhao, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jinque Luo, College of Pharmacy, Changsha Medical University, Changsha, China

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