Integrative Insights into Animal Models for Antihyperlipidemic Drug Screening: Bridging Preclinical and Translational Gaps in Research

Hyperlipidemia is a principal modifiable risk factor for atherosclerosis and cardiovascular disease, underscoring the critical need for predictive preclinical models to evaluate lipid-lowering therapies. Animal models are indispensable for elucidating lipid metabolism, validating pharmacological targets, and screening novel antihyperlipidemic agents prior to clinical translation. This integrative review presents an updated, critical synthesis of the animal models utilized in antihyperlipidemic drug screening, encompassing diet-induced, chemically induced, genetically modified, microbiota-modulated, and large-animal systems. Each model is evaluated based on its physiological relevance, methodological characteristics, and translational reliability. Small animals—such as mice, rats, and hamsters—provide accessible, cost-effective, and genetically versatile platforms for mechanistic investigations and early-stage screening. Conversely, larger species, including rabbits, pigs, and non-human primates, more accurately replicate human lipid profiles, atherosclerotic pathology, and cardiovascular physiology. Recent advancements in microbiota modulation, CRISPR-based genetic engineering, and multi-omics technologies have significantly enhanced mechanistic understanding and improved predictive accuracy in these models. By integrating classical and next-generation methodologies, this review proposes a translational framework designed to support ethical, reproducible, and clinically relevant preclinical research in lipid pharmacology.