Treatment of Obese Zebrafish with Saringosterol Acetate through AMP Activated Protein Kinase Pathway

Chem Biodivers. 2022 Sep;19(9):e202200495. doi: 10.1002/cbdv.202200495. Epub 2022 Aug 16.

Abstract

Object: Edible Brown Seaweed Sargassum fusiforme (Harvey) Setchell, 1931 abbreviated as Sargassum fusiforme was used for folk medical therapy in East Asia countries over five hundred years. Saringosterol acetate (SA) was isolated from S. fusiforme in our previous study and indicated various effects. However, anti-obesity activity of SA and its mechanism still unknown.

Method: The inhibitory effect of SA, isolated from S. fusiforme, on adipogenesis in 3T3-L1 adipocytes was investigated in vitro and in zebrafish model. Cell toxicity, differentiation, signaling pathway, and lipid accumulation of SA treated 3T3-L1 adipocytes were determined. The body weight and triglyceride content of diet-induced obese (DIO) adult male zebrafish were measured from 12 to 17 weeks after fertilization.

Result: SA attenuated the differentiation of cells and reduced lipid accumulation, and triglyceride content in the 3T3-L1 adipocytes. During the differentiation of adipocytes, SA suppressed fat accumulation and decreased the expression of signal factors responsible for adipogenesis. In SA-treated adipocytes, while fatty acid synthetase was downregulated, AMP-activated protein kinase (AMPK) was upregulated. Furthermore, SA suppressed body weight and triglyceride content in DIO zebrafish.

Conclusion: SA is a potential therapeutic agent in the management of metabolic disorders, such as obesity.

Keywords: Sargassum fusiformis; adipocytes; anti-obesity; saringosterol acetate.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases* / metabolism
  • Acetates / pharmacology
  • Adipogenesis
  • Animals
  • Body Weight
  • Diet, High-Fat
  • Fatty Acid Synthases / metabolism
  • Fatty Acid Synthases / pharmacology
  • Fatty Acid Synthases / therapeutic use
  • Male
  • Mice
  • Obesity / drug therapy
  • Stigmasterol / analogs & derivatives
  • Stigmasterol / pharmacology
  • Triglycerides / metabolism
  • Zebrafish* / metabolism

Substances

  • Acetates
  • Triglycerides
  • saringosterol
  • Stigmasterol
  • Fatty Acid Synthases
  • AMP-Activated Protein Kinases