Anti-Obesity Effects of Artocarpus integer Stem Bark Extract via Appetite and Lipid Metabolism Modulation in Obese Rats

Abstract

Obesity is a multifactorial metabolic disorder characterized by dysregulated energy homeostasis, impaired lipid metabolism, and altered hypothalamic appetite signaling. This study aimed to evaluate the anti-obesity effects and underlying mechanisms of a 95% ethanol extract of Artocarpus integer stem bark in a high-fat diet (HFD)-induced obese rat model. Obesity was induced in male Wistar rats using HFD feeding, followed by treatment with the extract (200–800 mg/kg/day, oral). Semaglutide and resveratrol were used as reference compounds. Body weight, food intake, adiposity, serum lipid profile, adipokines, histological changes, and gene expression related to lipid metabolism (Fas, Pparγ, Cpt-1, AdipoR1) and hypothalamic appetite regulation (Pomc, Mc4r, Npy) were evaluated. Phytochemical profiling was performed using LC–HRMS. The extract markedly reduced body weight gain, visceral adiposity, and food intake compared with the HFD control (p < 0.05), with the high-dose extract demonstrating a substantial weight-reducing effect that approached the magnitude of semaglutide. Treatment improved dyslipidemia by decreasing total cholesterol and triglycerides while increasing HDL levels. Adipokine imbalance was restored, as evidenced by reduced leptin and amylin and increased adiponectin levels. At the molecular level, the extract downregulated lipogenic genes (Fas, Pparγ), partially restored Cpt-1 expression, and normalized AdipoR1. In the hypothalamus, Pomc and Mc4r were upregulated, whereas Npy was suppressed. LC–HRMS analysis revealed the presence of stilbene, chalcone, and flavonoid derivatives. In conclusion, A. integer stem bark extract exerts anti-obesity effects through coordinated modulation of appetite signaling and lipid metabolism, supporting its potential as a multi-target phytotherapeutic agent for obesity management.