College of Agriculture & Natural Resources
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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item Changes in various metabolic parameters in blood and milk during experimental Escherichia coli mastitis for primiparous Holstein dairy cows during early lactation(Springer Nature, 2014-10-17) Moyes, Kasey M; Larsen, Torben; Sørensen, Peter; Ingvartsen, Klaus LThe objective of this study was to characterize the changes in various metabolic parameters in blood and milk during IMI challenge with Escherichia coli (E. coli) for dairy cows during early lactation. Thirty, healthy primiparous Holstein cows were infused (h = 0) with ~20-40 cfu of live E. coli into one front mammary quarter at ~4-6 wk in lactation. Daily feed intake and milk yield were recorded. At –12, 0, 3, 6, 12, 18, 24, 36, 48, 60, 72, 96, 108, 120, 132, 144, 156, 168, 180 and 192 h relative to challenge rectal temperatures were recorded and quarter foremilk was collected for analysis of shedding of E. coli. Composite milk samples were collected at -180, -132, -84, -36, -12, 12, 24, 36, 48, 60, 72, 84, 96, 132 and 180 h relative to challenge (h = 0) and analyzed for lactate dehydrogenase (LDH), somatic cell count, fat, protein, lactose, citrate, beta-hydroxybutyrate (BHBA), free glucose (fglu), and glucose-6-phosphate (G6P). Blood was collected at -12, 0, 3, 6, 12, 18, 24, 36, 60, 72, 84, 132 and 180 h relative to challenge and analyzed for plasma non-esterified fatty acids (NEFA), BHBA and glucose concentration. A generalized linear mixed model was used to determine the effect of IMI challenge on metabolic responses of cows during early lactation. By 12 h, E. coli was recovered from challenged quarters and shedding continued through 72 h. Rectal temperature peaked by 12 h post-challenge and returned to pre-challenge values by 36 h post-IMI challenge. Daily feed intake and milk yield decreased (P <0.05) by 1 and 2 d, respectively, after mastitis challenge. Plasma BHBA decreased (12 h; P <0.05) from 0.96 ± 1.1 at 0 h to 0.57 ± 0.64 mmol/L by 18 h whereas concentration of plasma NEFA (18 h) and glucose (24 h) were significantly greater, 11 and 27%, respectively, after challenge. In milk, fglu, lactose, citrate, fat and protein yield were lower whereas yield of BHBA and G6P were higher after challenge when compared to pre-challenge values. Changes in metabolites in blood and milk were most likely associated with drops in feed intake and milk yield. However, the early rise in plasma NEFA may also signify enhanced adipose tissue lipolysis. Lower concentrations of plasma BHBA may be attributed to an increase transfer into milk after IMI. Decreases in both milk lactose yield and % after challenge may be partly attributed to reduced conversion of fglu to lactose. Rises in G6P yield and concentration in milk after challenge (24 h) may signify increased conversion of fglu to G6P. Results identify changes in various metabolic parameters in blood and milk after IMI challenge with E. coli in dairy cows that may partly explain the partitioning of nutrients and changes in milk components after IMI for cows during early lactation.Item Transcriptional profiling and pathway analysis reveal differences in pituitary gland function, morphology, and vascularization in chickens genetically selected for high or low body weight(Springer Nature, 2019-04-25) Ellestad, Laura E.; Cogburn, Larry A.; Simon, Jean; Le Bihan-Duval, Elisabeth; Aggrey, Samuel E.; Byerly, Mardi S.; Duclos, Michel J.; Porter, Tom E.Though intensive genetic selection has led to extraordinary advances in growth rate and feed efficiency in production of meat-type chickens, endocrine processes controlling these traits are still poorly understood. The anterior pituitary gland is a central component of the neuroendocrine system and plays a key role in regulating important physiological processes that directly impact broiler production efficiency, though how differences in pituitary gland function contribute to various growth and body composition phenotypes is not fully understood.Item Diet induced the change of mtDNA copy number and metabolism in Angus cattle(Springer Nature, 2020-07-21) Bai, Ying; Carrillo, José A.; Li, Yaokun; He, Yanghua; Song, JiuzhouGrass-fed and grain-fed Angus cattle differ in the diet regimes. However, the intricate mechanisms of different beef quality and other phenotypes induced by diet differences are still unclear. Diet affects mitochondrial function and dynamic behavior in response to changes in energy demand and supply. In this study, we examined the mtDNA copy number, mitochondria-related genes expression, and metabolic biomarkers in grass-fed and grain-fed Angus cattle. We found that the grass-fed group had a higher mtDNA copy number than the grain-fed group. Among different tissues, the mtDNA copy number was the highest in the liver than muscle, rumen, and spleen. Based on the transcriptome of the four tissues, a lower expression of mtDNA-encoded genes in the grass-fed group compared to the grain-fed group was discovered. For the mitochondria-related nuclear genes, however, most of them were significantly down-regulated in the muscle of the grass-fed group and up-regulated in the other three tissues. In which, COX6A2, POLG2, PPIF, DCN, and NDUFA12, involving in ATP synthesis, mitochondrial replication, transcription, and maintenance, might contribute to the alterations of mtDNA copy number and gene expression. Meanwhile, 40 and 23 metabolic biomarkers were identified in the blood and muscle of the grain-fed group compared to a grass-fed group, respectively. Integrated analysis of the altered metabolites and gene expression revealed the high expression level of MDH1 in the grain-fed group might contribute to the mitochondrial NADH oxidation and spermidine metabolism for adapting the deletion mtDNA copy number. Overall, the study may provide further deep insight into the adaptive and regulatory modulations of the mitochondrial function in response to different feeding systems in Angus cattle.Item O-GLCNACYLATION IS NOT INCREASED IN THE HYPOTHALAMUS OF RATS GIVEN 6 WEEK ACCESS TO SUCROSE SOLUTION DESPITE MARKERS OF METABOLIC DYSREGULATION(2018) Hudgins, Samantha Morgan; Castonguay, Thomas W; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The peptide hormone leptin acts globally to maintain various metabolic processes. Impaired response to leptin binding is referred to as leptin resistance and results in metabolic dysregulation. Leptin is essential in the prevention of weight gain through central signals to increase energy expenditure and reduce food intake. A sugar sensitive pathway, the hexosamine biosynthesis pathway (HBP), may be the cause of diet induced leptin resistance. The HBP glycosylates proteins by modifying fructose- 6-phosphate molecules from glycolysis. While high sugar diets have been linked to leptin resistance, O-GlcNAcylation of pathway proteins have not been examined. Approximately 8-week-old male rats were assigned to ad libitum access to diet and water or 30% sucrose solution, diet and water. On Day 5 rats were surgically fitted with a third ventricle cannula. On Day 41, diet and sugar solutions were removed for an overnight fast. On Day 42 each rat received a central injection of leptin or control solution and subsequently euthanized 30 minutes post injection. Body weight and body composition were not significantly different between treatment groups after 42 days. However, the Sucrose group exhibited signs of metabolic syndrome, evidenced by increased fasting serum triglycerides and glucose as well as decreased serum HDL. Analysis of hypothalamic O-GlcNAcylation revealed no significant difference between treatment groups. These data may be the result of variability of glucose utilization within the hypothalamus. These data support previous findings that 42-day access to a 30% sucrose solution yields evidence of metabolic syndrome in the absence of obesity as well as the absence of increased hypothalamic OGlcNAcylation. Future research should examine O-GlcNAcylation regionally within the hypothalamus. Analysis of protein specific O-GlcNAcylation was not achieved; however, a novel O-GlcNAcylation was observed in hypothalamic tissue at the Threonine 1808 residue of prolow-density lipoprotein receptor-related protein 1 isoform X1 (LRP-1), a protein that may play a crucial role in leptin signaling. These data give further evidence to support the use of 30% sucrose solution to model leptin resistance in Sprague Dawley rats, as well as provide a target protein for future analysis.Item METABOLIC CHANGES ASSOCIATED WITH ANDROGEN INDEPENDENT GROWTH IN A MOUSE MODEL OF PROSTATE CANCER(2014) Martin, Philip Lloyd; Samal, Siba; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)PTEN and TP53 loss are common molecular alterations in aggressive prostate cancer that progresses to castrate resistant prostate cancer (CRPC). PTEN/TP53 loss contributes to regulation of self-renewal and differentiation in prostate progenitor cells, the presumptive tumor and metastasis initiating cells for prostate cancer. TP53 plays an important role in regulating normal cellular metabolism, and loss of function is responsible for metabolic alterations in tumor cells, including increased aerobic glycolysis. We use a novel model of Pten/Tp53 deleted prostate cancer to investigate properties of tumor and metastasis initiating cells, and metabolic alterations that contribute to the evolution of CRPC. We employed a genetically engineered mouse model of Pten-/-Tp53-/- prostate cancer to develop an orthotopic model derived from a clonal cell line from the parental heterogeneous prostate carcinoma. We used histopathology and immunohistochemistry to characterize the orthotopic primary tumors and metastases. We performed metabolomic screening followed by focused analysis of HK II enzyme levels, activity, and cellular distribution in androgen replete and androgen deprived tumors. We also compared HK II levels in primary and metastatic human prostate cancer. Tumor heterogeneity was due to transformation of tumor and metastasis initiating cells with biphenotypic potential capable of basal and luminal differentiation. There was epithelial-to-mesenchymal transition (EMT) in cells of the luminal lineage. The model was capable of androgen independent growth, which influenced the differentiation of metastasis initiating cells. CRPC had increased reliance on glycolysis with increased cytoplasmic and mitochondrial-associated HK II. These metabolic adaptations afforded CRPC increased ability to withstand metabolic stress. HK II levels in human metastases were markedly increased compared to primary tumors. Pten/Tp53 loss in prostate cancer contributes to lineage plasticity in both tumor and metastasis initiating cells, contributing to heterogeneity observed in primary tumors and metastases. Increased glycolysis due to increased total and mitochondrial HK II is a metabolic adaptation that contributes to the evolution of aggressive disease, with progression to androgen independence, providing increased energy and carbon precursors for anabolic processes. Mitochondrial bound HK II blocks apoptosis and contributes to survival in the androgen deprived environment. Targeting this metabolic adaptation may provide improved treatment for this deadly disease.Item Investigation of chicken embryo metabolism and substrate utilization during later development(2013) Hu, Qiong; Bequette, Brian J; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The objective of this research was to determine metabolic adaptations and substrate utilization during chicken embryo development and to determine the influence of breeder age and egg size on embryonic growth and metabolism during development (embryonic day 11 to posthatch day 1). In Study One, for both small (n = 60, 53.2 ± 1.04 g) and large (n = 60, 69.0 ± 1.86 g) eggs from 26 versus 42 wk-old broiler breeders, glucose content in albumen decreased to negligible levels by embryonic day (e) 11 whereas mannose and fucose remained constant. Higher yolk glucose content was observed in small eggs from e17 onwards whereas proportions of yolk linoleic and linolenic acids were greater in larger eggs. Liver adenosine monophosphate protein kinase (AMPK), the central cellular energy-sensor, was higher in activity in embryos from large eggs, and AMPK activity was at its highest for both sizes of eggs on e14. These observations suggest that glucose was consumed in early development (before e11). Lower liver AMPK activity and higher yolk glucose at later stages in small eggs from young hens suggests that anaplerotic metabolism is enhanced to alleviate the relative nutrient deficiency. In Study Two, a gas chromatography-mass spectrometry-based metabolomic profiling approach was employed to investigate effects of hen age and egg size on embryo metabolism. Principal component analysis of liver and blood metabolites showed separate clusters on both e14 and e20 from 32 and 51 wk-old hens. The separate clusters featured branched-chain amino acid, glycine, serine and threonine metabolism. Clear separation of metabolites was not observed for embryos from small versus large eggs at any developmental age. Breeder age had a larger influence on embryo metabolism and growth. Three clusters corresponding to liver metabolites from e14, e17 and e20 embryos formed a sub-tree that merged with the cluster from posthatch day 1 chicks in the Hierarchical clustering analysis. This result confirmed that embryo metabolism adapted during later development. Embryos from 51 wk-old hens displayed predominant developmental changes in ketone, glycerolipid and glutathione metabolic pathways in the liver compared to 32 wk-old hens. Study Three aimed to quantify gluconeogenesis, and substrate utilization and partition in e14 and e19 embryos. A constant infusion protocol (8 h) was developed for delivery of [U-13C] glucose and [U-13C] glycerol into the chorio-allantoic fluid. Gluconeogenesis was higher in e19 compared to e14 embryos, consistent with the need for increased liver and muscle glycogen by e19 embryos in preparation for emergence. The contribution of glucose to non-essential amino acid (NEAA) synthesis was greater in e14 vs e19 embryos, indicating a higher demand for amino acids for tissue growth. Glycerol contributed very little (< 5%) to gluconeogenesis; thus the remainder must be ascribed to amino acids. Relatively more of acetyl-CoA flux was derived from fatty acid metabolism in e14 embryos compared to 3-carbon pool substrates. In summary, this thesis research established aspects of embryo metabolism and nutrient partition in developing embryos that previously were unknown. This included demonstration of a role of AMPK in development, the influence of breeder age on global embryo metabolism, and metabolic adaptations in gluconeogenesis, Krebs cycle activity and glycerol metabolism during the latter half of chicken embryo development.