Enhanced Anti-Obesity Efficacy of Orlistat via Co-Administration with Iron Oxide Nanoparticles (SPIONs) in a High-Fat Diet–Induced Obese Mice Model

نویسندگان

1 Department of Biology, College of Science, University of Misan, Maysan, Iraq

2 Department of Biology, College of Science, University of Misan, Maysan, Iraq

3 Department of Biology, College of Science, University of Misan, Maysan, Iraq

doi
10.22052/JNS.2026.01.089
چکیده

Obesity is a chronic, progressive condition associated with dyslipidemia, insulin resistance, and a proinflammatory state. Orlistat, a lipase inhibitor, is approved for weight management but has limited efficacy and side effects. Superparamagnetic iron oxide nanoparticles (SPIONs) have been reported to modulate lipid metabolism–related gene expression. This study aimed to evaluate whether co-administration of iron oxide nanoparticles enhances the lipid-lowering effects of orlistat in an obese mouse model. Seventy adult male mice (20–25 g) were divided into five groups (n = 14 each): (A) control (standard diet + saline), (B) obese (high-fat diet, no treatment), (C) obese + orlistat (120 mg/kg/d), (D) obese + SPIONs (dose proportional to body weight), and (E) obese + orlistat + SPIONs. Treatments were administered orally (0.2 mL/d) for 21 days. Seven mice per group were sacrificed on days 7 and 21. Serum triglycerides (TG), total cholesterol (CH), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) were measured using commercial kits. One-way ANOVA with LSD post hoc test was performed; P < 0.05 was considered significant. Compared to controls, obese mice exhibited significantly elevated TG, CH, and LDL (P < 0.05) and decreased HDL (P < 0.05). Orlistat alone (group C) reduced TG marginally (136.2 ± 32.6 mg/dL) compared to obese (151.6 ± 27.3 mg/dL) but did not significantly alter CH or LDL levels. SPIONs alone (group D) produced a slightly greater TG reduction (125.9 ± 31.8 mg/dL) than orlistat (P > 0.05) and significantly decreased HDL relative to orlistat (P < 0.05). The combination (group E) decreased TG (133.7 ± 30.3 mg/dL) and VLDL more than orlistat alone (P > 0.05) but had no additive effect on CH, LDL, or HDL. VLDL levels remained statistically similar across all groups (P > 0.05). Co-administration of SPIONs with orlistat modestly improved TG and VLDL levels compared to orlistat alone but did not significantly affect CH, LDL, or HDL within 21 days. These findings suggest that SPIONs may potentiate certain lipid-lowering effects of orlistat. Further studies optimizing dose, treatment duration, and nanoparticle functionalization are warranted to clarify mechanistic pathways and long-term metabolic benefits.