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

BMB Rep. 2023 Apr;56(4):246-251. doi: 10.5483/BMBRep.2022-0211.

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 antiobesity agent, which impedes adipogenesis and improves glucose homeostasis. Tschimganidine can then be evaluated for clinical application as a therapeutic agent. [BMB Reports 2023; 56(4): 246-251].

Publication types

  • News

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism
  • Adipocytes / metabolism
  • Adipogenesis
  • Animals
  • Anti-Obesity Agents* / metabolism
  • Anti-Obesity Agents* / pharmacology
  • Anti-Obesity Agents* / therapeutic use
  • Diabetes Mellitus, Type 2* / metabolism
  • Diet, High-Fat / adverse effects
  • Lipids
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy
  • Obesity / metabolism

Substances

  • AMP-Activated Protein Kinases
  • tschimganidin
  • Anti-Obesity Agents
  • Lipids

Grants and funding

ACKNOWLEDGEMENTS 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-2021 M3A9E4021818 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).