Annona muricata Leaf Extract Improves Metabolic Biomarkers and Tissue-Specific Lipid Metabolism in Diet-Induced Obese Mice

Introduction

Altered lipid metabolism drives obesity-associated metabolic dysfunction and hepatic steatosis. Although Annona muricata has shown promising metabolic effects, the molecular mechanisms underlying these effects remain unclear. This study evaluated the effects of A. muricata leaf extract on metabolic biomarkers and tissue-specific changes related to lipid metabolism in diet-induced obese mice.

Methods

Male BALB/c mice (n = 42) were randomly allocated to six experimental groups: normal diet (ND), high-fat diet (HFD), HFD supplemented with Annona muricata leaf extract (250 or 500 mg/kg; HFD-AM250 and HFD-AM500), HFD plus metformin (HFD-MET), and a transition group (TRANS). Obesity was induced by HFD feeding for 8 weeks followed by 6 weeks of treatment. Serum glucose, triglycerides, HDL-cholesterol, ALT, AST, and hepatic steatosis were evaluated. Relative expression of Ampk, Pparα, Pparγ, Srebf1, and Fasn was determined in liver, whereas Ampk, Pparγ, C/ebpα, and Fabp4 were analyzed in adipose tissue by RT-qPCR. Data were analyzed using ANOVA or Kruskal–Wallis tests.

Results

Compared with untreated HFD mice, Annona muricata leaf extract (500 mg/kg) significantly improved metabolic biomarkers by reducing serum glucose, triglycerides, ALT and AST activities while increasing HDL-cholesterol (all p < 0.05). Treatment also markedly attenuated hepatic steatosis (6.3 ± 2.3% vs. 21.1 ± 3.1% in HFD mice). In the liver, the extract increased Ampk and Pparα expression while decreasing Pparγ, Srebf1, and Fasn. In adipose tissue, treatment increased Ampk expression and decreased Pparγ, C/ebpα, and Fabp4 expression (all p < 0.05).

Conclusions

Annona muricata leaf extract improved metabolic biomarkers and attenuated hepatic steatosis, accompanied by tissue-specific changes associated with lipid metabolism in the liver and adipose tissue. These findings suggest that A. muricata leaf extract has potential as a bioactive nutritional intervention for improving obesity-associated metabolic dysfunction.