Browsing by Subject "Lipidomics"
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Item Effects Of Algae Feeding On Mouse Metabolome(2017-09) Ma, YiweiAlgae have been investigated and developed as a source of food, dietary supplement, and biofuel, due to their chemical and nutrient composition. Algae consumption carries algal proteins, polyunsaturated fatty acids (PUFAs), vitamins, dietary fibers, and bioactive compounds into the biological systems of humans and animals, and therefore are expected to elicit metabolic and physiological responses. Numerous efforts have been undertaken to understand the health-promoting effects of algae consumption, such as their hypolipidemic, antioxidant, anti-obesity and anti-cancer properties. However, the metabolic events in algae-elicited effects were not examined in details in spite of the fact that these benefits are largely based on the metabolic interactions between algal components and the biological system. In this study, the influences of consuming green algae (Scenedesmus sp.) on the metabolic status of young mice was investigated through growth performance, blood chemistry, and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. Compared to the control diet, 5% algae promoted growth performance while 20% algae suppressed it. The growth performance was significantly increased by 5% algae but decreased by 20% algae feeding. Serum glucose, triacylglycerols (TAG), and blood urea nitrogen (BUN) levels were not affected by both treatments, but serum cholesterol level was dramatically decreased by 20% algae feeding. Metabolomic analysis of liver, serum, feces and urine samples revealed diverse influences of algae feeding on mouse metabolome, which are represented by the features as follows: 1). Urinary vitamins and fecal pigments are identified as robust exposure markers of algae feeding. 2). Despite the high-level protein in algae, the impacts of algae feeding on free amino acids in serum and the liver were quite limited. 3). Algae feeding increased the PUFA levels in serum and liver lipidomes and the free fatty acids in feces. 4). 5% algae increased the level of reduced glutathione (GSH) in the liver while 20% algae increased the level of oxidized glutathione (GSSG) in the liver and the levels of aldehydic lipid oxidation products (LOPs) in the liver and urine. 5). 5% algae selective increased the levels of intermediate metabolites, including adenosine monophosphate (AMP), adenylsuccinic acid, dephospho-CoA, and nicotinamide, in the liver while 20% algae increased the levels of carnitine and carnitine derivatives in the liver. 6). Algae feeding dramatically altered the microbial metabolism, as reflected by the increases in short-chain fatty acids (SCFAs) and primary bile salts in feces, the increases of branched fatty acids in urine, the decreases of secondary bile acids in feces, and the decrease of p-cresol metabolites in urine. Overall, multiple correlations between metabolite markers and growth performance in algae feeding were established in this study and could serve as a foundation for further mechanistic investigations on the biological effects of algae feeding.Item Resolving the major dyslipidemia phenotypes and genetic risk factors for familial hyperlipidemia in Miniature Schnauzers(2022-09) Tate, NicoleHyperlipidemia is common in the Miniature Schnauzer breed, especially those over the age of 10. Hyperlipidemia is defined as an increased concentration of lipids (i.e., triglycerides and/or cholesterol) in the blood. Hyperlipidemia predisposes Miniature Schnauzers to severe consequences such as pancreatitis, gallbladder mucoceles, and glomerular proteinuria. However, the underlying molecular derangements and cause remains unresolved. It is suspected that hyperlipidemia in Miniature Schnauzers is due to an underlying genetic risk factor(s). Additionally, the varied responses to management strategies in the breed, suggests a potential for multiple subtypes. Thus, the goal of this thesis was to identify the spectrum of dyslipidemia subtypes and ascertain the metabolic and genetic risk factors underlying hyperlipidemia in Miniature Schnauzers. The possibility of multiple dyslipidemia subtypes within the breed was evaluated using lipoprotein profile data and unsupervised hierarchical cluster analysis. The results support the hypothesis that multiple dyslipidemia subtypes exist in Miniature Schnauzers and that the major distinguishing factor between the subtypes may be differences in low-density lipoproteins. Additional studies are warranted to confirm the range and number of distinct lipoprotein profiles within this breed. The lipidome and metabolome of Miniature Schnauzers with moderate-to-severe primary hyperlipidemia were compared to those from Miniature Schnauzers with normal serum triglyceride concentrations to elucidate the underlying pathophysiological processes of hyperlipidemia in the breed. Differences in the lipidome and metabolome were identified between the two groups. The differentiating lipid and metabolite species suggest involvement and/or disruption of the pathways and products of glycerolipid, glycerophospholipid, glycosphingolipid, and fatty acid metabolism. The results of this study provide insights into the underlying pathways. However, it is still unknown whether these pathways are causal of hyperlipidemia or if the disturbances are in response to elevated triglyceride (TG) concentrations. This thesis also used unsupervised hierarchical cluster analysis to compare the lipidome and metabolome of Miniature Schnauzers dogs with normal serum triglyceride concentrations, mild triglyceride elevations, moderate-to-severe triglyceride elevations, and triglyceride elevations due to endocrinopathies (i.e., secondary hyperlipidemia). The most notable finding being that Miniature Schnauzers with mild HTG cannot be definitively classified as having primary HTG, as their lipid disturbances do not reliably differ from dogs with NTG. Whole genome sequencing (WGS) of eight Miniature Schnauzers with primary hyperlipidemia was screened for risk variants in six HTG candidate genes: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. A monogenic cause for primary hyperlipidemia in the breed was not identified in the evaluated candidate genes. Two variants passed the filtering criteria, a deletion in the TATA box of APOE and a missense variant in GPIHBP1. While the two variants did not have sufficient evidence to support a strong impact, neither can be ruled out as contributors to the disease. These findings, and the growing data on dyslipidemia subtypes in Miniature Schnauzers, suggest that hyperlipidemia in the breed is likely a polygenic or complex trait. Finally, a key challenge in genetic studies is the prioritization of identified variants. Many in silico tools have been developed to use features of amino acids and proteins to determine if a variant is likely pathogenic. However, these methods are typically trained using human variants and have not been validated for use in non-human species. Thus, this thesis evaluates the performance of eight tools for pathogenicity prediction of missense variants (MutPred2, PANTHER, PhD-SNP, PolyPhen2-HumDiv, PolyPhen2-HumVar, Provean, SIFT, and SNPs&GO) for use in the dog and horse. The findings of this study suggest that these methods can be effectively used in veterinary species.