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

Abstract

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 ultrahigh-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.

A multimodal analytical method to simultaneously determine monoacetyldiacylglycerols, medium and long chain triglycerides in biological samples during routine lipidomics

“…As previously alluded to, the relative abundance of fragment corresponding to sn-2 FA is lower compared to sn-1 FA fragment45 . In a similar fashion, the fragments at m/z 239 24. and m/z 265.25 were diagnostic of fatty acid ketene ions [16:0 + H-H2O] + and [18:0 +H-H2O] + respectively, with the relative abundance of the sn-2 FA ketene ion higher than the sn-1 FA ketene ion (Fig.…”

“…5a).Assignment of the sn-1, sn-2 and sn-3 FAs of scTG 16:0/18:0/4:0 was based on the relative abundance of these fragments with sn-1 FA > sn-2 FA > sn-3 FA, a trend typical of TG species26,28 . Furthermore, diagnostic fatty acid ketene ions at m/z 239 24. and m/z 265.26 correspond to [16:0 + H-H2O] + and [18:1 +H-H2O] + , which is representative of sn-1 FA and sn-2 FA respectively (Fig.…”

Comparison of critical biomarkers in 2 erectile dysfunction models based on GEO and NOS-cGMP-PDE5 pathway

“…It was reported that inbred Fisher 344 rats were more metabolically sensitive than outbred Sprague Dawley strain. [ 63 ] That may be the reason that Fisher 344 strain was chosen for DMED model. [ 9 ] Furthermore, some research demonstrated that different rat strains respond to injury differently, and thus in preclinical neurotrauma studies, strain influence is an important consideration during evaluation of outcomes.…”

Silica nanoparticles induce hepatocyte ferroptosis and liver injury via ferritinophagy

“…12 month old F344 rats were selected as animal model because studies have shown that F344 rat strain had a more sensitive liver metabolic response and non-heme iron accumulated in liver tissues with age, which might be helpful in observing hepatocyte ferroptosis characterized by iron homeostasis imbalance. [28][29][30][31][32][33][34] All rats were fed in an environment of 20-24 °C temperature, humidity of 40-60%, 12/12 hours light/dark cycle, and given a normal diet.…”