title: 1H NMR-based lipidomics of rodent fur: species-specific lipid profiles and SCD1 inhibitor-related dermal toxicity.
abstract: A method is described that allows noninvasive identification and quantitative assessment of lipid classes present in sebaceous excretions in rodents. The method relies on direct high-field proton NMR analysis of common group lipid protons in deuterated organic solvent extracts of fur. Extracts from as little as 15 mg of fur from rat, mouse, and hamster provided acceptable results on a 600 MHz NMR equipped with a cryogenically cooled proton-observe probe. In rats, sex- and age-related differences in lipid composition are larger than differences in fur collected from various body regions within an individual and much larger than interanimal differences in age- and sex-matched specimens. The utility of this method to noninvasively monitor drug-induced sebaceous gland atrophy in rodents is demonstrated in rats dosed with a stearoyl-CoA desaturase 1 (SCD1) inhibitor. In this model, a 35% reduction in sebum lipids, extracted from fur, was observed. Finally, structural elucidation of cholesta-7,24-dien-3β-ol ester as the most prominent, previously unidentified sebum sterol ester in male Syrian hamsters is described. The utility of this method for drug and cosmetic safety and efficacy assessment is discussed.
authors.affiliation: Applied and Investigative Metabolomics Group, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Purnima
authors.initials: P
authors.lastname: Khandelwal
authors.affiliation: Applied and Investigative Metabolomics Group, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Steven
authors.initials: S
authors.lastname: Stryker
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Hannguang
authors.initials: H
authors.lastname: Chao
authors.affiliation: Applied and Investigative Metabolomics Group, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Nelly
authors.initials: N
authors.lastname: Aranibar
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Lawrence
authors.affiliation: Discovery Biology, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Malavi
authors.initials: M
authors.lastname: Madireddi
authors.affiliation: Discovery Biology, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Discovery Biology, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Luping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Applied and Investigative Metabolomics Group, Bristol-Myers Squibb Company, Princeton, NJ.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Reily
mesh_terms: D000076203:Animal Fur / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D017207:Rats, Sprague-Dawley; D012625:Sebaceous Gland Diseases / Q000139:chemically induced / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; C000594769:stearoyl-CoA desaturase SCD-1, rat
keywords: NMR assay; fur lipid; fur sebum; hamster sebum; human sebum; lipid class measurement; metabolomics; mouse sebum; rat sebum; sebum lipid; skin lipid; stearoyl-CoA desaturase 1
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