Using liquid chromatography mass spectrometry (LC-MS) to assess the effect of age, high-fat diet, and rat strain on the liver metabolome

• Published in: PloS one Vol. 15; no. 7; p. e0235338
• Main Authors: Boyce, Greg, Shoeb, Mohammad, Kodali, Vamsi, Meighan, Terence, Roberts, Jenny R, Erdely, Aaron, Kashon, Michael, Antonini, James M
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.07.2020; Public Library of Science (PLoS)
• Subjects: Age; Age factors; Biology and Life Sciences; Carboxylic acids; Chromatography; Data processing; Diet; Fatty acids; Glucose; High fat diet; High performance liquid chromatography; Inbreeding; Intermediates; Ions; Laboratory animals; Lipid metabolism; Lipids; Liquid chromatography; Liver; Liver research; Mass spectrometry; Mass spectroscopy; Medical examination; Medicine and Health Sciences; Metabolism; Metabolites; Metabolomics; NMR; Nuclear magnetic resonance; Obesity; Occupational safety; Physical Sciences; Principal components analysis; Proteins; Research and Analysis Methods; Rodents; Scientific imaging; Spectroscopy; Triglycerides; Variance analysis; United States; West Virginia; United States > US; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0235338

The goal of this study was to use liquid chromatography mass spectrometry to assess metabolic changes of two different diets in three distinct rat strains. Sprague-Dawley, Fischer 344, and Brown-Norway male rats were maintained on a high-fat, or regular diet for 24 weeks. Liver tissue was collected at 4, 12, and 24 weeks to assess global small molecule metabolite changes using high resolution accurate mass spectrometry coupled to ultra-high-performance liquid chromatography. The results of the global metabolomics analysis 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 significantly changing metabolites than that of age for the Brown Norway and Fisher 344 strains, whereas diet had the greatest influence in the Sprague Dawley strain only at the 4-week time point. As expected, metabolites involved in lipid metabolism were changed in the animals maintained on a high fat diet compared to the regular diet. There were also significant changes observed in the concentration of Tri carboxylic acid cycle intermediates that were extracted from the liver of all three strains based on diet. The results of this study showed that a high fat diet caused significant liver and metabolic changes compared to a regular diet in multiple rat strains. The inbred Fisher 344 and Brown Norway rats were more metabolically sensitive to the diet changes than outbred Sprague Dawley strain. The study also showed that age, as was the case for Sprague Dawley, is an important variable to consider when assessing metabolic changes.