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Profiling across species for the identification of optimal animal models of dyslipidemia
Author(s) -
Strack Alison M,
CarballoJane E,
Mendoza V H,
Gagen K,
McNamara L,
Gorski J,
Eiermann G,
Petrov A,
Akiyama T,
Kulick A,
Donnelly M,
Voronin G,
Rosa R,
Cumiskey AM,
Bekkari K,
Mitnaul L,
Puig O,
Koblan K S,
Hubbard Brian K
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.628.5
Subject(s) - dyslipidemia , hamster , simvastatin , biology , rodent , cholesterol , lipidomics , hyperlipidemia , lipidome , bioinformatics , computational biology , pharmacology , endocrinology , obesity , diabetes mellitus , ecology
In an attempt to understand the predictivity of various animal models for study of dyslipidemia, we analyzed lipid and metabolic profiles across 5 mouse strains, 6 other non‐primate species and 4 primates. Plasma fatty acid composition, lipoproteins and phospholipoproteins were examined through lipidomics and additional metabolic parameters. Given the importance of statins as therapeutics in humans, 2‐week responsiveness to simvastatin was assessed in each model. When examining the relative proportion of lipids contained within the 3 major lipid biosynthetic pathways, the species that most reflect humans are primates and hamsters. When absolute levels of cholesterol and other lipids are measured, most historical literature models for atherosclerosis and dyslipidemia (mouse and rabbit) fall out of the range of humans; primates, pig, dog, and hamster are the models that most resemble humans. Subsequent dendogram analyses of the 8 lipid classes measured demonstrated primates clustered together most closely to humans, followed by dog and hamster. Most non‐rodent species exhibited decreases in plasma cholesterol and other lipids in response to simvastatin. Overall, primates are the model that most reflects humans. For practical utility in routine studies, the data point to the hamster and dog as potential models for target validation and lead identification. Research supported by Merck Research Labs.