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Browsing by Subject "Lipid"

Now showing 1 - 6 of 6
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    An Apple from the Tree? A Look at Cardiometabolic Risk Factors in Parents and Offspring
    (2015-06) Halvorsen, Tanya
    Objectives: To relate parental cardiometabolic risk factors with corresponding values in their children and assess the influence of adiposity on these associations. Study Design: Associations of adiposity, blood pressure, lipids, fasting insulin and glucose, and a risk factor cluster score were evaluated in a cross sectional study of 179 parents and their children (6-18 years, N=255). Insulin resistance was assessed by euglycemic clamp in parents and children aged 10 or older. Metabolic syndrome in parents was defined by ATPIII criteria. Cluster scores of the risk factors were created based on age-specific z-scores. Analyses included Pearson correlation and linear regression, adjusted for parent and child age, sex, race, and body mass index (BMI), accounting for within-family correlation. Results: We found positive parent-child correlations for measures of adiposity (BMI, BMI percentile, waist, subcutaneous fat, and visceral fat; r=0.22-0.34, all p≤0.003), systolic blood pressure (SBP) (r=0.20, p=0.002), total cholesterol (r=0.39, p<0.001), low-density lipoprotein cholesterol (r=0.34, p<0.001), high density lipoprotein cholesterol (r=0.26, p<0.001) triglycerides (r=0.19, p=0.01) and insulin sensitivity (r=0.22, p=0.02) as well as cluster scores (r=0.15, p=0.02). After adjustment for BMI all parent-child correlations, except systolic blood pressure, remained significant. Conclusions: Although adiposity is strongly correlated between parents and children, many cardiometabolic risk factors correlate independent of parent and child BMI. Adverse parental cardiometabolic profiles may identify at-risk children independent of the child’s adiposity status.
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    Discovery of a new species of Heterococcus and analysis of its lifecycle, genome, and lipid production
    (2012-09) Nelson, David Roy
    A new species of Xanthophyceae, Heterococcus coloradii, was discovered among snow fields in the Rocky Mountains. Axenic cultures of H. coloradii were prepared, and their cellular morphology, growth, and accumulation of lipids were characterized. H. coloradii was found to grow at temperatures approaching freezing and to accumulate large intracellular stores of lipids. Of particular interest was the accumulation of several long-chain polyunsaturated fatty acids known to be important for human nutrition such as eicosapentaenoic acid and palmitoleic acid. Algae that accumulate lipids in this manner have potential uses as sources of biofuels and poly-unsaturated fatty acids for human nutrition. In order to study H. coloradii's repertoire of genes, genomic DNA was extracted and sequenced with the Illumina GAIIx. 72 base-pair reads were organized into a draft genome of 170 mega base-pairs with 20x coverage. Over 20,000 unique protein hits were received with a MegaBLASTp using the translated draft genome as a query. Many genes were found that are involved in lipid metabolism and cold tolerance, thus highlighting the unique biology of H. coloradii.
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    HDL-Mimetic Peptides as Potential Therapeutics for Alzheimer's Disease
    (2018-08) Chernick, Dustin
    Alzheimer’s disease (AD) is the leading cause of dementia worldwide, for which there currently exists no approved disease modifying treatment. A number of large scale human clinical studies have confirmed a robust connection between high density lipoprotein (HDL) – known as the ‘good cholesterol’ levels and AD. Low levels of HDL are associated with increased risk and severity of AD. The role of HDL in the brain is not fully established, however, the anti-inflammatory and anti-oxidative properties of HDL are thought to be critical for its beneficial effects. Apolipoprotein E (apoE) is a key constituent of HDL-like particles in the interstitial fluid (ISF) and cerebral spinal fluid (CSF) in the brain. ApoE exists in 3 common variants in the human population (apoE2, E3, and E4), and the apoE4 isoform is the strongest genetic risk factor for AD, accounting for 40-60% of cases. This risk allele is known to increase neuroinflammation and to promote the aggregation and deposition of amyloid beta (Aβ) in the brain, effects which are influenced by the poor lipidation status of apoE4 (incomplete or improper composition of HDL-like particles) in the brain. Previous studies in the laboratory of Dr. Ling Li have shown that overexpression of human apoA-I, the primary apolipoprotein associated with HDL in the periphery, mitigated amyloid pathology and rescued memory deficits in AD mice. However, a full-length, glycosylated protein is extremely difficult and costly to synthesize and to administer. Therefore, the goal of my research was to test the therapeutic potential of small HDL-mimetic peptides, designed to mimic the beneficial function of their parent apolipoproteins, in AD. My studies focused on 4F, an 18 amino acid HDL-mimetic peptide that has been shown to be safe and well tolerated in human clinical trials for cardiovascular disease. I have demonstrated that the lipidation state of apoE is negatively impacted by the addition of aggregated Aβ to astrocytes from mice and humans, in vitro, an effect that is reversed by the addition of 4F. In addition, I confirmed that apoE4 is less lipidated than apoE2 and E3 at baseline, and demonstrated that apoE4 is more susceptible to the detrimental effects of Aβ on lipidation than apoE2. Intriguingly, 4F was able to completely rescue this effect, bringing apoE4 lipidation levels on par with those of apoE2, even in the presence of Aβ. Preliminary in vivo studies in mice expressing the human apoE isoforms and in a mouse model of AD indicate that 4F reduces soluble amyloid levels in the brain and attenuates memory deficits. As chronic neuroinflammation is a key hallmark of AD pathology, another line of my research focused on a small molecule, called Minnelide. Minnelide is a water soluble, pro-drug of triptolide, which is an anti-inflammatory agent that has been shown in Dr. Li’s lab and in other labs to mitigate AD pathology and rescue memory deficits in animal models. Poor solubility hinders this agent’s prospects in the clinic, and so we sought to test the efficacy of Minnelide in AD. My studies show that Minnelide attenuated age-related cognitive decline in AD mice, independent of Aβ levels in the brains of these animals. These data, taken together, indicate that HDL mimetic peptides, and targeting of inflammatory pathways in the periphery and in the brain are promising avenues for continued efforts to find an effective treatment for AD.
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    The Role Of Acyl-Coa Thioesterase 1 In Hepatic Lipid Metabolism
    (2017-05) Franklin, Mallory
    The liver is an essential organ for maintaining homeostasis and is vital for storage, synthesis, oxidation, and recirculation of lipid in fed and fasted states. In response to fasting, fatty acids (FAs) flux from adipose tissue to the liver and are converted to acyl-CoAs for incorporation into complex lipids or transportation into the mitochondria for oxidation. The latter process is orchestrated by a group of proteins that are transcriptional targets of peroxisome proliferator activated receptor α (PPARα). However, little is known about hepatic acyl-CoA thioesterase 1 (ACOT1), a member of the broader acyl-CoA thioesterase family that catalyzes the conversion of acyl-CoAs back to FAs and coenzyme A. Thus, this research is aimed to understand the role of ACOT1 in fasting lipid metabolism. To investigate its physiological importance, we employed adenovirus-mediated knockdown, overexpression in tissue culture, as well as generation of a whole-body Acot1 knockout mouse line. Our results show that ACOT1 preferentially hydrolyzes acyl-CoA molecules that are destine for mitochondrial β-oxidation. As such, acute Acot1 knockdown results in reduced liver triglyceride (TG) and enhanced FA oxidation in vivo and in vitro. Increased FA oxidation correlated to greater hepatic glucose production and storage. Additionally, we determined that ACOT1 regulates PPARα by providing FA ligands. As such, supplementation with a PPARα synthetic ligand rescues the Acot1 knockdown phenotype. Furthermore, Acot1 overexpression increases PPARα activity only when ACOT1 is catalytically active. Together these data suggest that ACOT1 regulates PPARα through its hydrolysis product. We also discovered that ACOT1 translocates to the nucleus during prolonged fasting, potentially to provide a local pool of FAs to activate PPARα. Thus, acute Acot1 knockdown solicits enhanced FA oxidation, yet reduces PPARα target gene expression. Complications of this disconnect between metabolism and gene expression was evident by increased oxidative stress and inflammation, often seen in fibrotic and cirrhotic stages of non-alcoholic fatty liver disease (NAFLD), when Acot1 was knocked down. To further our investigation of ACOT1, we compared whole-body Acot1 knockout mice to their wild type littermates. We demonstrate that Acot1 knockout lead reduces adiposity, by decreasing adipocyte size and increasing adipocyte number. Acot1 knockout also reduced hepatic TG, providing protection from oxidative stress and inflammation that precedes TG accumulation. However, Acot1 knockout reduced glucose tolerance suggesting impaired glucose homeostasis. These results suggest Acot1 knockout impaired lipid storage potential, increasing lipid intermediates, and contributing to glucose intolerance. Taken together, hepatic ACOT1 regulates FA oxidation and protects from oxidative stress and inflammation, whereas whole-body ACOT1 contributes to lipid storage.
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    Role Of Dietary Factors On Nutrient Excretion And Manure Characteristics Of Growing Pigs
    (2016-02) Luo, Zhaohui
    In the U.S. pork industry, feed represents the largest proportion of the total production cost. Therefore, pork producers are continually trying to improve feed efficiency and reduce feed cost. This has become more important because the prices of conventional feed ingredients, including corn and soybean meal, has increased dramatically in recent years. As a result, the addition of increased amount of high fiber ingredients such as corn distillers dried grains with solubles (DDGS) and soybean hulls (SBH) to swine diets, and processing diets to achieve a smaller particle size have become common practices. However, manure foam accumulation on the surface of anaerobic deep pits on commercial swine farms has been a coincidental problem in recent years, and the potential cause has been associated with changes in diet composition. As a result, a better understanding of the connection between swine diet composition and nutrient excretion and manure foaming is critical for developing long-term mitigation strategies. Based on the theory of “froth flotation”, foam formation requires 3 contributing factors, including biogas production, surfactants, and stabilizers, which may come from undigested nutrients in the manure. Results from studies have suggested that specific undigested nutrients in the manure may serve as surfactants (lipids and long-chain fatty acids; LCFAs) and stabilizers (small particles) as well as substrates to produce biogas (fiber and protein) in foam formation. This evidence suggest that adding DDGS and SBH in swine diets may increase overall manure output due to higher levels of indigestible fiber, resulting in more dry matter (DM) and nutrients in manure. In addition, smaller particle size of diets may result in a greater concentration of stabilizers in the manure. As a result, methods to maximize feed digestibility and minimize nutrient excretion appear to be essential for reducing manure pit foaming. The research described in this thesis addressed the effects of feeding alternative feed ingredients (DDGS with variable oil content and SBH) with different particle size on nutrient excretion and manure characteristics of growing pigs. Results in Chapter 2 suggested that manure foaming capability (MFC) was impacted by diet particle size and fiber source. Greater MFC were only observed for pigs fed coarsely ground SBH diet. The relatively high concentration of soluble fiber in the soybean hulls diet compared with DDGS, which contains a high concentration of insoluble fiber, appears to have a greater effect on MFC. In addition, increased DM excretion and changes in manure pH resulting from diet composition were 2 significant factors that contributed to MFC. Results in Chapter 3 suggested that manure foaming does not occur when evaluating fresh manure samples, indicating that microbial fermentation is essential for manure foam formation. Further studies are encouraged to compare the microbial ecology between samples of foaming manure and non-foaming manure. In conclusion, when diets are coarsely ground, manure from pigs fed diets containing significant amounts of soluble fiber source tend to have greater MFC after fermentation. These results suggest that diet formulation strategies to maximize DM digestibility and reduce DM excretion by reducing diet particle size, along with minimizing the amount coarsely ground SBH in diets will decrease manure foaming incidence in anaerobic manure pits.
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    Utilization of oil crop residues for enhanced algae based production of lipids, polyunsaturated fatty acids, and protein
    (2013-12) Wang, Zhen
    Microalgae are capable of synthesizing many high value compounds, such as lipids, polyunsaturated fatty acids (PUFAs), and proteins, and therefore considered potential feedstock for production of biodiesel, nutraceuticals, and animal feeds. The synthesis and accumulation of lipids, PUFAs, and proteins are influenced by such factors as microalgae strain, trophic conversion mode of growth, nutrient supply, and light and temperature conditions. Regulation of these factors must take cost issue into account. The goal of this research was to investigate the use of oil crop biomass residue (OCBR), a low-cost material from oil extraction plants, to cultivate specific algae strains for targeted production of lipids, PUFAs, and proteins. The specific objectives of present thesis were: 1) to optimize the conditions for acid hydrolysis of OCBR for best yield and desirable profile of nutrients; 2) to evaluate microalgae growth on different OCBR media; 3) to characterize the chemical compositions especially the lipid, protein and EPA contents in the harvested algal biomass as affected by culture media; 4) to study the effect of temperature and growth phase on algae EPA synthesis.The one-factor-at-a-time experimental design was used to optimize the acid hydrolysis conditions based on the key nutrient level including the total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (COD) and ammonia nitrogen (NH4-N) in the hydrolysates. The optimal conditions were found to be using 3 % sulfuric acid and hydrolyzing residues at 90 °C for 20 hrs. The hydrolysates (OCBR media) produced under the optimal conditions were used to cultivate two algae strains, namely UM258 and UM268. The results from 5 days of cultivation showed that the best OCBR media supported faster algae growth than artificial media, with maximal algal biomass yield of 2.7 g/L and 3 g/L, respectively. Moreover, the total lipids after 5 days cultivation for UM258 and UM268 were 54 % and 35%, respectively. The OCBR also promoted protein accumulation in UM 268 compared with artificial media. Temperature-time interaction-effect on EPA synthesis was observed. Temperature of 20 °C and time of longer than 6 days of cultivation (after algae reach stationary phase), were found optimal for EPA accumulation for UM258 with EPA reaching 18% in total fatty acids. The results suggest that OCBR media are an excellent alternative for algae growth and have great potential for large scale productions of algae based ingredients for biodiesel, high value foods and animal feeds.