Targeted metabolomic profiling in rat tissues reveals sex differences

Abstract

Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermediary metabolism and evidence for any sex differences. To clarify the sex-specific activities of liver, heart and kidney tissues, we used targeted metabolomics, linear discriminant analysis (LDA), principal component analysis (PCA), cluster analysis and linear correlation models to evaluate sex and organ-specific differences in amino acids, free carnitine and acylcarnitine levels in male and female Sprague-Dawley rats. Several intra-sex differences affect tissues, indicating that metabolite profiles in rat hearts, livers and kidneys are organ-dependent. Amino acids and carnitine levels in rat hearts, livers and kidneys are affected by sex: male and female hearts show the greatest sexual dimorphism, both qualitatively and quantitatively. Finally, multivariate analysis confirmed the influence of sex on the metabolomics profiling. Our data demonstrate that the metabolomics approach together with a multivariate approach can capture the dynamics of physiological and pathological states, which are essential for explaining the basis of the sex differences observed in physiological and pathological conditions.

Sexual Dimorphism in Energy Metabolism of Wistar Rats Using Data Analysis

“…This indicates that exercising males increase their need for amino acids to fuel energy needs, whereas females increase their mobilization of fat, thereby requiring less alternative fuels such as carbohydrate and amino acids [16]. Substrate availability during exercise appears to modulate the amino acid oxidation differences between sexes [17][18][19]. The aim of our study was to reveal the main variances in energy metabolism using liquid chromatography-tandem mass spectrometry-based targeted metabolomics' measurements in the blood plasma of healthy male and female Wistar rats.…”

Proteomics Reveals that Methylmalonyl-CoA Mutase Modulates Cell Architecture and Increases Susceptibility to Stress

“…Actually, no significant difference in the NR uptake levels was observed between propionate-treated cells and the respective untreated controls (e.g., propionate-incubated MUT-KO vs. untreated MUT-KO-0 h time point). Moreover, results from this assay showed no significant differences between the three cell types (WT, MUT-KO, and MUT-Rescue) at each tested propionate concentration (10 and 25 mM) and time point (24,48, and 72 h). Accordingly, a 10 mM concentration showed no significant effect even in the MTT assay, while 25 mM of propionate at 48 and 72 h caused a significant reduction in MTT absorbance of MUT-KO cells when compared with untreated controls (0 h time point) and with the other cell types (WT and MUT-Rescue).…”

Exercise with food withdrawal at thermoneutrality impacts fuel use, the microbiome, AMPK phosphorylation, muscle fibers, and thyroid hormone levels in rats

“…Serum (10 µl) of each sample was transferred on a filter paper card and dried overnight to obtain a dried blood spot (DBS) at room temperature (Ruoppolo et al, ). The metabolites were extracted from DBS and esterified as previously described (Ruoppolo et al, ).…”