The overnight (16-h) fast is one of the most common experimental manipulations performed in rodent studies. Despite its ubiquitous employment, a comprehensive evaluation of metabolomic and transcriptomic sequelae of fasting in conjunction with routine clinical pathology evaluation has not been undertaken. This study assessed the impact of a 16-h fast on urine and serum metabolic profiles, transcript profiles of liver, psoas muscle, and jejunum as well as on routine laboratory clinical pathology parameters. Fasting rats had an approximate 12% relative weight decrease compared to ad libitum fed animals, and urine volume was significantly increased. Fasting had no effect on hematology parameters, though several changes were evident in serum and urine clinical chemistry data. In general, metabolic changes in biofluids were modest in magnitude but broad in extent, with a majority of measured urinary metabolites and from 1/3 to 1/2 of monitored serum metabolites significantly affected. Increases in fatty acids and bile acids dominated the upregulated metabolites. Downregulated serum metabolites were dominated by diet-derived and/or gut-microflora derived metabolites. Major transcriptional changes included genes with roles in fatty acid, carbohydrate, cholesterol, and bile acid metabolism indicating decreased activity in glycolytic pathways and a shift toward increased utilization of fatty acids. Typically, several genes within these metabolic pathways, including key rate limiting genes, changed simultaneously, and those changes were frequently correlative to changes in clinical pathology parameters or metabolomic data. Importantly, up- or down-regulation of a variety of cytochrome P450s, transporters, and transferases was evident. Taken together, these data indicate profound consequences of fasting on systemic biochemistry and raise the potential for unanticipated interactions, particularly when metabolomic or transcriptomic data are primary end points.

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This article is available online at http://www.jlr.org fetal development ( 2 ). The composition of sebum is highly species specifi c ( 2 ) and can be affected by both systemic and environmental perturbations, including bacterial invasion ( 3 ), oral agents that affect lipid biosynthesis ( 5 ), skin disease ( 2, 6, 7 ), and toxicity ( 8,9 ). Inasmuch as sebaceous glands are a prominent component of mammalian skin, sebum composition and excretion rates are one measure of overall skin health. It is desirable to have a noninvasive method for measuring these parameters to support safety or effi cacy assessments in pharmaceutical or cosmetic research where either skin sensitivity may be a concern or sebum reduction is the target.Traditionally, many analytical methods for sebum assessment have been reported. These can be divided into two groups based on whether they 1 ) distinguish individual lipid molecules or 2 ) measure lipid classes independent of the exact FA substituents. Previously, we described an NMR spectroscopy-based method that falls into the second category for assessing the molecular constitution of sebum and compared this with other analytical approaches ( 5 ). The NMR method relies on accurate integration of specifi c protons on selected analytes in extracts of skin biopsies and absorbent fi lms commonly used in clinical evaluation of sebum excretion. The fundamental advantage of this method is that by integrating a peak from a single headgroup proton (or protons) arising from a class of lipids (e.g., the H3 of esterifi ed cholesterol), one can assess the molar concentration of the entire class, independent of the FA distribution. In contrast, chromatographic-or mass spectrometric-based methods must contend with multiple (up to dozens) of individual analytes within the class that have different masses and physical properties. In this work, we extend its utility to fur clippings that can be obtained noninvasively for use in preclinical studies. Abstract A method is described that allows noninvasive identifi cation and quantitative assessment of lipid classes present in sebaceous excretions in rodents. The method relies on direct high-fi eld 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 protonobserve 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 sexmatched 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-3 ␤ -ol ester as the most prominent, previously unidentifi ed ...