Annona muricata leaf extract attenuates hepatic lipogenesis and adipogenesis

Food Funct. 2021 May 21;12(10):4621-4629. doi: 10.1039/d1fo00509j. Epub 2021 Apr 28.


Annona muricata (graviola) is a medicinal plant that can be used to alleviate chronic human diseases by providing antioxidants and inducing immunomodulation. In this study, we found that treatment of AML12 hepatocytes with steam (SGE) and ethanol (EGE) extracts of graviola leaf downregulated the expression of fatty acid (FA) oxidation genes, including ACOX1, CPT1, and PPARα, with no change in the expression of FA synthesis genes. However, whereas EGE inhibited the differentiation and lipid accumulation of 3T3-L1 adipocytes and downregulated FA synthesis genes, no similar changes were observed in response to treatment with SGE. In an in vivo experiment using mice fed a high-fat diet (HFD), body weight was reduced in response to treatment with EGE, which also dose-dependently alleviated liver hepatocyte ballooning induced by the consumption of a HFD. However, genes involved in FA oxidation and the secretion of very low density lipoprotein (VLDL) were downregulated. We also found that the size of adipocytes was reduced in response to EGE treatment, and that there was a downregulated expression of genes involved in adipogenesis and FA synthesis. Furthermore, we detected increases in the levels of cholesterol in the plasma, whereas ALT activity was reduced. Collectively, these results indicates that EGE inhibits lipid influx into the liver and adipogenesis in adipose tissues. These bioactive properties of EGE indicate its potential as a natural ingredient that can be used to prevent obesity.

MeSH terms

  • 3T3-L1 Cells
  • Acyl-CoA Oxidase / genetics
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adipogenesis / genetics
  • Animals
  • Annona / chemistry*
  • Cell Differentiation / drug effects
  • Diet, High-Fat
  • Down-Regulation
  • Gene Expression Regulation / drug effects
  • Lipid Metabolism
  • Lipogenesis / drug effects*
  • Lipogenesis / genetics
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR alpha
  • Plant Extracts / pharmacology*


  • PPAR alpha
  • Plant Extracts
  • ACOX1 protein, mouse
  • Acyl-CoA Oxidase