Using Liquid Chromatography Mass Spectrometry (LC-MS) to Assess the Effect of Age, Diet, and Rat Strain on the Global Metabolome

Details

• Personal Author:
  Antonini J ; Boyce G ; Erdely A ; Kodali V ; Meighan T ; Roberts J ; Shoeb M
• Description:
  The exposome encompasses the entire environmental exposures of an individual during a lifetime. These exposures include diet, lifestyle, environmental toxins, and workplace exposures. The interactions of combined exposures can lead to exacerbation of disease. The goal of this study was to use liquid chromatography mass spectrometry (LC-MS) to assess metabolic changes in three distinct animal strains based on two different diets. Sprague-Dawley (SD), Fischer 344 (F344), and Brown-Norway (BN) male rats were maintained on a high fat, Western (HF), or regular diet for 24 weeks. Serum was collected at 4, 12, and 24 weeks to assess metabolite changes. A cold methanol buffer was used to extract metabolites. Metabolite extracts were analyzed using high resolution accurate mass (HRAM) mass spectrometry coupled to ultra-high performance liquid chromatography. The results of the global metabolomics revealed significant changes based on both age and diet within all three strains. Principal component analysis revealed that the influence of diet caused a greater variation in the significantly changing metabolites (p< 0.05) than that of age for the BN and F344 strains, while the SD strain showed a large influence from diet at the 4 week time point. As expected, metabolites involved in lipid metabolism and bile acid formation were upregulated in the animals maintained on a HF diet compared to the regular diet. There were also significant changes observed in acetyl-coA concentrations between the two diets at all of the time points for all strains. A targeted LC-MS/MS quantification of TCA cycle intermediates was performed on liver metabolite extracts. The results of this targeted analysis revealed significant increases in alpha-ketoglutarate, succinyl-coA, and fumarate for the HF diet across all three strains. The BN strain showed a significant increase in malate in the HF diet compared to the regular diet, whereas the SD strain had a significantly higher concentration of citrate in the liver of the HF diet than the other two strains. The results of this study show that Sprague-Dawley showed greater metabolic variability to diet changes than Fisher 344 or Brown Norway strains. It also shows that age is an important experimental variable to consider when performing metabolic studies. [Description provided by NIOSH]
• Subjects:
  Acids Age Factors Diet Energy Metabolism Environmental Exposure Enzymes Laboratories Lipids Longevity Occupational Exposure Occupational Health Safety Toxicology

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• Keywords:
  Age Factors Amino Acids Analytical Instruments Biochemical Indicators Biological Effects Environmental Exposure Exposure Assessment Exposure Levels Fats Laboratory Animals Laboratory Testing Lifespan Liquid Chromatography Liver Mass Spectrometry Metabolic Effects Metabolic Study Metabolism Metabolites Molecular Signaling Occupational Exposure Proteins Serology

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  463-464
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20055073
• Citation:
  Toxicologist 2019 Mar; 168(1):463-464
• CAS Registry Number:
  Citric acid (CAS RN 77-92-9) ; Fumaric acid (CAS RN 110-17-8) ; L-Glutamic acid (CAS RN 56-86-0) ; Maleic acid (CAS RN 110-16-7)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9bca25574a786506e39ab94cfd1300f618d19ac37844b5b36173d94bca144dfdd94a2bc3f16cb5c37455c0bf0dda90e783707eb1cfc7322bc204ce08bea5b560
• Download URL:
  https://stacks.cdc.gov/view/cdc/217450/cdc_217450_DS1.pdf
• File Type:
  [PDF - 907.93 KB ]