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Tschimganidine reduces lipid accumulation through AMPK activation and alleviates high-fat diet-induced metabolic diseases

  • Min-Seon Hwang (Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Yonsei University) ;
  • Jung-Hwan Baek (Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Yonsei University) ;
  • Jun-Kyu Song (Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Yonsei University) ;
  • In Hye Lee (Department of Life Science, College of Natural Science, Ewha Womans University) ;
  • Kyung-Hee Chun (Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Yonsei University)
  • Received : 2022.12.29
  • Accepted : 2023.01.10
  • Published : 2023.04.30

Abstract

Obesity increases the risk of mortality and morbidity because it results in hypertension, heart disease, and type 2 diabetes. Therefore, there is an urgent need for pharmacotherapeutic drugs to treat obesity. We performed a screening assay using natural products with anti-adipogenic properties in 3T3-L1 cells and determined that tschimganidine, a terpenoid from the Umbelliferae family, inhibited adipogenesis. To evaluate the anti-obesity effects of tschimganidine in vivo. Mice were fed either a normal chow diet (NFD) or a high-fat chow diet (HFD) with or without tschimganidine for 12 weeks. Treatment with tschimganidine decreased lipid accumulation and adipogenesis, accompanied by reduced expression of adipogenesis and lipid accumulation-related factors. Tschimganidine significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased that of AKT. Depletion of AMPK relieved the reduction in lipid accumulation resulting from tschimganidine treatment. Moreover, tschimganidine administration drastically reduced the weight and size of both gonadal white adipose tissue (WAT) and blood glucose levels in high-fat diet-induced obese mice. We suggest that tschimganidine is a potent anti-obesity agent, which impedes adipogenesis and improves glucose homeostasis. Tschimganidine can then be evaluated for clinical application as a therapeutic agent.

Keywords

Acknowledgement

This study was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2021M3A9E4021818 and NRF-2022M3A9G8082639), and Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C0153, Republic of Korea).

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