Obesity is a highly prevalent chronic disease, and lifestyle-based interventions often show limited long-term efficacy. Nanotechnology has emerged as a preclinical strategy to improve the bioavailability, stability, tissue delivery, and metabolic activity of anti-obesity agents. This systematic review evaluated the effects of nanostructure-based interventions in diet-induced obese murine models. Following PRISMA guidelines, searches of PubMed, Web of Science, and Scopus identified 26 eligible in vivo studies that included obese control groups and assessed obesity-related outcomes, including body weight, adiposity, fat mass, food intake, metabolic regulation, and related molecular pathways. Across heterogeneous nanoplatforms, nano-enabled interventions generally reduced body weight, adiposity, fat mass, adipose tissue accumulation, or obesity-associated metabolic dysfunction compared with obese controls. The reported mechanisms involved modulation of lipid metabolism, stimulation of fatty acid ß-oxidation, inhibition of adipocyte differentiation, induction of browning-related thermogenic pathways, improvement of glucose¿lipid homeostasis, and attenuation of inflammatory, oxidative, and endoplasmic reticulum stress signaling. However, these findings should be interpreted cautiously because the included studies differed substantially in nanomaterial composition, physicochemical properties, active compounds, route of administration, dose, treatment duration, obesity-induction protocol, and outcome assessment. In addition, the SYRCLE risk-of-bias assessment showed frequent unclear judgments in core methodological domains, particularly those related to randomization, allocation concealment, housing conditions, and blinding procedures. Several studies also provided limited information on animal characteristics, biodistribution, tissue accumulation, long-term safety, and toxicity. Overall, current evidence suggests that nanostructure-based anti-obesity interventions are biologically promising proof-of-concept strategies in preclinical murine models, rather than approaches ready for clinical translation. Future studies should incorporate standardized physicochemical characterization, transparent reporting of animal and experimental conditions, comparative head-to-head designs, biodistribution profiling, and long-term toxicity assessment before these platforms can be advanced toward human metabolic applications.
