Yin, W, et al., Plasma Lipid Profiling across Species for the Identifi Cation of Optimal Animal Models of Human Dyslipidemia. Journal of Lipid Research, 2011. 53(51-65.
Metabolon results led to:
- Understanding lipidomic profiles of plasma lipids in 24 commonly used animal models across various animals species including dyslipidemic humans under basal and simvistatin-treated conditions
- Characterization of applicability of different animal models to dyslipidemic humans
- Identification of optimal animal models(s) for target validation and drug discovery for developing treatments for dyslipidemia
Key metabolomic observations:
- Fatty acid composition of phosphatidylcholine was stable across animal species and dietary conditions
- Omega-6 fatty acids were the main source of fatty acids in plasma cholesterol esters (CEs) and the nonessential fatty acids provided the majority of fatty acids in triglycerides (TG) and phosphatidylcholine (PC)
Although statins reduce risk of cardiovascular disease (CVD), a residual risk still remains for adverse coronary events and development of new strategies has been hampered by fidelity of preclinical animal models. Thus, a lipidomic analysis of plasma lipids in 24 commonly used animal models and dyslipidemic humans under basal and simvistatin-treated conditions was completed. The response of non-human primates (excepting marmosets) was most similar to dyslipidemic humans and thus the best model to study disease mechanism and validation of potential drug targets. The dog is best suited for developing pharmacological agents to lower low density lipoprotein – cholesterol containing (LDL-c) particles. The dog, hamster on high fat diet and db/db mice are likely the best model to validate targets related to secondary CVD risks such as high non-high density lipoprotein (non-HDL) and high TG. Thus, this demonstrates the utility of metabolomics for delineating sensitive and specific differences in preclinical models to inform about the choice of animal model, and thus, the potential utility of this approach in many therapeutic areas.