Obesity is associated with metabolic abnormalities that increase the risk and severity of several diseases. This study aimed to explore whether the aqueous extract of Annona squamosa Linn leaves (ASE) can ameliorate metabolic abnormalities associated with high fat (HF) diet-induced
obesity. Forty-eight male Wistar rats were distributed among four treatment groups: a standard
low-fat diet group, a HF diet group, and two HF diet groups with a daily oral dose of ASE (100 or 200 mg/kg
body weights) administered for 9 weeks. Daily energy intake,
body weight,
blood glucose levels and
glucose tolerance, and
insulin tolerance were evaluated. At the end of the study, organs, and tissues were collected and weighed for analysis, and blood samples were collected to determine the serum
insulin levels and serum liver
enzymes. Total phenolic and
flavonoid contents and
2,2-Diphenyl-1-picrylhydrazyl free radical antioxidant activity of the ASE were evaluated.
Oral administration of the low dose of ASE to HF diet-fed rats significantly reduced the long-term food intake and
body weight gain without altering adiposity compared with untreated HF diet-fed rats. This outcome was accompanied by a significant improvement in
insulin sensitivity and a reduction in fasting
blood glucose (FBG) levels measured at weeks 6 and 9 of the study. The high dose of ASE had a short-term effect on
body weight gain and food and caloric intake, and in the long-term, it improved FBG levels measured at weeks 6 and 9 of the study. The high dose of ASE resulted in
hyperinsulinemia and high homeostatic model assessment for
insulin resistance (HOMA-IR) value compared to healthy rats. Total phenolic and
flavonoid contents were 74.9 ± 0.491 mg of
gallic acid equivalent and 20.0 ± 0.091 mg
quercetin equivalent per g of ASE, respectively. The
antioxidant activity of ASE expressed as half-maximal inhibitory concentration (IC50) value was 8.43 ± 0.825 mg/mL. These data suggest that ASE can safely and potently reduce the development of
insulin resistance induced by HF diet feeding and lowering
body weight gain in a dose-dependent manner.