Molecular, Genetic, and Biochemical Nutrition Commons^™

Therapeutic Potential Of Garlic Chive-Derived Vesicle-Like Nanoparticles In Nlrp3 Inflammasome-Mediated Inflammatory Diseases, Baolong Liu, Xingzhi Li, Han Yu, Xuan Shi, You Zhou, Sophie Alvarez, Michael J. Naldrett, Stephen D. Kachman, Seung-Hyun Ro, Xinghui Sun, Soonkyu Chung, Lili Jing, Jiujiu Yu

Department of Nutrition and Health Sciences: Faculty Publications

Aberrant activation of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome drives the development of many complex inflammatory diseases, such as obesity, Alzheimer’s disease, and atherosclerosis. However, no medications specifically targeting the NLRP3 inflammasome have become clinically available. Therefore, we aim to identify new inhibitors of the NLRP3 inflammasome in this study. Methods: Vesicle-like nanoparticles (VLNs) were extracted from garlic chives and other Allium vegetables and their effects on the NLRP3 inflammasome were evaluated in primary macrophages. After garlic chive-derived VLNs (GC-VLNs) were found to exhibit potent anti-NLRP3 inflammasome activity in cell culture, …

Associations Of Dietary Lipid-Soluble Micronutrients With Hepatic Steatosis Among Adults In The United States, Weiwen Chai, Sarah Eaton, Heather E. Rasmussen, Meng Hua Tao

Department of Nutrition and Health Sciences: Faculty Publications

Lipid-soluble micronutrients may be beneficial to non-alcoholic fatty liver disease due to their important roles in metabolism and maintaining tissue functions. Utilizing 2017–2018 National Health and Nutrition Examination Survey, this study examined the potential overall and race/ethnicity-specific (black, Hispanic and white) associations of dietary lipid-soluble micronutrients (α-tocopherol, retinol, vitamin D, β-carotene and total carotenoids) with hepatic steatosis. The analysis included 4376 adults (1037 blacks, 981 Hispanics, 1549 whites) aged ≥20 years who completed the transient elastography examination with dietary data available. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regressions. The age-adjusted prevalence of steatosis was …

Skeletal Muscle Cell Growth Alters The Lipid Composition Of Extracellular Vesicles, Taylor R. Valentino, Blake D. Rule, C Brooks Mobley, Mariana Nikolova-Karakashian, Ivan Jose Vechetti Jr

Department of Nutrition and Health Sciences: Faculty Publications

We sought to characterize the lipid profile of skeletal muscle cell-derived Extracellular Vesicles (EVs) to determine if a hypertrophic stimulus would affect the lipid composition of C2C12 myotube-derived EVs. Analyses included C2C12 murine myoblasts differentiated into myotubes and treated with Insulin-Like Growth Factor 1 (IGF-1) for 24 h to induce hypertrophic growth. EVs were isolated from cell culture media, quantified using Nanoparticle Tracking Analysis (NTA) and analyzed using Transmission Electron Microscopy (TEM). EVs were homogenized and lipids extracted for quantification by Mass Spectrometry followed by downstream lipid class enrichment and lipid chain analysis. IGF-1 treatment elicited an increase in CD63 …

Multi-Assay Nutritional Metabolomics Profiling Of Low Vitamin A Status Versus Adequacy Is Characterized By Reduced Plasma Lipid Mediators Among Lactating Women In The Philippines: A Pilot Study, Catherine M. Johnson

Master's Theses

Background: A significant portion of lactating women in less developed countries have vitamin A (VA) deficiency. Lactation has substantial effects on a mother’s metabolism and VA is known to be needed in multiple biological processes, including growth, vision, immunity, and reproduction.

Objective: The objective of this pilot study was to utilize metabolomics profiling to conduct a broad, exploratory assessment of differences in plasma metabolites associated with low VA status versus adequacy in lactating women.

Methods: Plasma samples from lactating women who participated in a survey in Samar, Philippines, were selected from a cross-sectional study based on plasma retinol concentrations indicating …

Sars-Cov-2 Concentrations In A Wastewater Collection System Indicated Potential Covid-19 Hotspots At The Zip Code Level, Renys E. Barrios, Chin Lim, Megan S. Kelley, Xu Li

Department of Nutrition and Health Sciences: Faculty Publications

Wastewater based epidemiology (WBE) has been successfully applied for SARS-CoV-2 surveillance at the city and building levels. However, sampling at the city level does not provide sufficient spatial granularity to identify COVID-19 hotspots, while data from building-level sampling are too narrow in scope for broader public health application. The objective of this study was to examine the feasibility of using wastewater from wastewater collection systems (WCSs) to monitor COVID-19 hotspots at the zip code level. In this study, 24-hr composite wastewater samples were collected from five manholes and two wastewater treatment plants (WWTPs) in the City of Lincoln, Nebraska. By …

Bovine Mammary Alveolar Mac-T Cells Afford A Tool For Studies Of Bovine Milk Exosomes In Drug Delivery, Mojisola Ogunnaike

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Bovine milk exosomes (BMEs) have attracted attention as vehicles for delivering RNA therapeutics. BMEs originate in mammary alveolar cells. Here, we determined whether bovine mammary alveolar MAC-T cells are a promising tool to assess RNA delivery by BMEs. MAC-T cells exosomes (MAC-T BMEs) and BMEs were harvested by differential ultracentrifugation. Exosome size, morphology, microRNA content and marker proteins were assessed using nanoparticle tracking analysis, transmission electron microscopy, real-time PCR and immunoblot analysis, respectively. MAC-T cells were genetically engineered to secrete MAC-T BMEs endogenously labeled with a near-infrared fluorescent protein and tissue distribution was compared to fluorophore-labeled BMEs following intravenous injection …

Ruminant Milk-Derived Extracellular Vesicles: A Nutritional And Therapeutic Opportunity?, Siew Ling Ong, Cherie Blenkiron, Stephen Haines, Alejandra Acevedo-Fani, Juliana A.S. Leite, Janos Zempleni, Rachel C. Anderson, Mark J. Mccann

Department of Nutrition and Health Sciences: Faculty Publications

Milk has been shown to contain a specific fraction of extracellular particles that are reported to resist digestion and are purposefully packaged with lipids, proteins, and nucleic acids to exert specific biological effects. These findings suggest that these particles may have a role in the quality of infant nutrition, particularly in the early phase of life when many of the foundations of an infant’s potential for health and overall wellness are established. However, much of the current research focuses on human or cow milk only, and there is a knowledge gap in how milk from other species, which may be …

Carotenoid-Rich Brain Nutrient Pattern Is Positively Correlated With Higher Cognition And Lower Depression In The Oldest Old With No Dementia, Jirayu Tanprasertsuk, Tammy M. Scott, Aron K. Barbey, Kathryn Barger, Xiang-Dong Wang, Mary Ann Johnson, Leonard W. Poon, Rohini Vishwanathan, Nirupa R. Matthan, Alice H. Lichtenstein, Guylaine Ferland, Elizabeth R. Johnson

Department of Nutrition and Health Sciences: Faculty Publications

Background: Healthy dietary patterns are related to better cognitive health in aging populations. While levels of individual nutrients in neural tissues are individually associated with cognitive function, the investigation of nutrient patterns in human brain tissue has not been conducted.

Methods: Brain tissues were acquired from frontal and temporal cortices of 47 centenarians from the Georgia Centenarian Study. Fat-soluble nutrients (carotenoids, vitamins A, E, K, and fatty acids [FA]) were measured and averaged from the two brain regions. Nutrient patterns were constructed using principal component analysis. Cognitive composite scores were constructed from cognitive assessment from the time point closest to …

Effect Of The Lysosomotropic Agent Chloroquine On Mtorc1 Activation And Protein Synthesis In Human Skeletal Muscle, Michael S. Borack, Jared M. Dickinson, Christopher S. Fry, Paul T. Reidy, Melissa M. Markofski, Rachel R. Deer, Kristofer Jennings, Elena Volpi, Blake B. Rasmussen

All Faculty Scholarship for the College of Education and Professional Studies

Background

Previous work in HEK-293 cells demonstrated the importance of amino acid-induced mTORC1 translocation to the lysosomal surface for stimulating mTORC1 kinase activity and protein synthesis. This study tested the conservation of this amino acid sensing mechanism in human skeletal muscle by treating subjects with chloroquine—a lysosomotropic agent that induces in vitro and in vivo lysosome dysfunction.

Methods

mTORC1 signaling and muscle protein synthesis (MPS) were determined in vivo in a randomized controlled trial of 14 subjects (10 M, 4 F; 26 ± 4 year) that ingested 10 g of essential amino acids (EAA) after receiving 750 mg of chloroquine …

Palmitoleate Protects Against Zika Virus-Induced Placental Trophoblast Apoptosis, Philma Glora Muthuraj, Aryamav Pattnaik, Prakash K. Sahoo, Md Torikul Islam, Asit K. Pattnaik, Siddappa N. Byrareddy, Corrine K. Hanson, Ann Anderson Berry, Stephen D. Kachman, Sathish Kumar Natarajan

Department of Nutrition and Health Sciences: Faculty Publications

Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted …

Effect Of Serine-Dipeptide Bacterial Lipid Treatment On Gene Expression In Hepg2 Liver Cells, Shaharia Ferdus

Honors Scholar Theses

While greater abundances of Bacteroidetes are associated with better health outcomes, this phylum is a major producer of serine-dipeptide lipids, which are thought to promote inflammation via Tolllike receptor (TLR) stimulation. Lipid 654 (L-654) is one class of serine-dipeptide lipids that has been isolated from arterial plaques and is thought to contribute to atherogenesis. Recent evidence shows that not only does long-term L-654 exposure attenuate atherosclerosis, it also significantly reduces hepatic lipid levels and markers of inflammation in mice. To better understand the impact on the human liver, L-654 was administered to HepG2 hepatocytes at concentrations of 0.5 μg/mL or …

An Intron Variant Of The Gli Family Zinc Finger 3 (Gli3) Gene Differentiates Resistance Training-Induced Muscle Fiber Hypertrophy In Younger Men, Christopher G. Vann, Robert W. Morton, Christopher B. Mobley, Ivan J. Vechetti, Brian K. Ferguson, Cody T. Haun, Shelby C. Osburn, Casey L. Sexton, Carlton D. Fox, Matthew A. Romero, Paul A. Roberson, Sara Y. Oikawa, Chris Mcglory, Kaelin C. Young, John J. Mccarthy, Stuart M. Phillips, Michael D. Roberts

Department of Nutrition and Health Sciences: Faculty Publications

We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with …

The Analysis Of Folate-Dependent Transcription Factor Zinc Finger Protein 410, Feifan Xu

Senior Honors Theses

A previous study that introduced dietary folate to mice in the form of folic acid to determine if gene activity would be altered based on this biological molecule demonstrated that mice without folic acid had cognition deficits, and this phenomenon was correlated with altered gene expression in their brains. The included bioinformatic analysis revealed two main transcription factors that bind to proteins in the nucleus, and one is known as the Zinc Finger Protein 410 (Zfp410). Due to the lack of literature explaining the function of this transcription factor, this project is intended to analyze Zfp410 in detail from scratch. …

Early Satellite Cell Communication Creates A Permissive Environment For Long-Term Muscle Growth, Kevin A. Murach, Bailey D. Peck, Robert A. Policastro, Ivan J. Vechetti, Douglas W. Van Pelt, Cory M. Dungan, Lance T. Denes, Xu Fu, Camille R. Brightwell, Gabriel E. Zentner, Esther E. Dupont-Versteegden, Christopher I. Richards, Jeramiah J. Smith, Christopher S. Fry, John J. Mccarthy, Charlotte A. Peterson

Department of Nutrition and Health Sciences: Faculty Publications

Using in vivo muscle stem cell (satellite cell)-specific extracellular vesicle (EV) tracking, satellite cell depletion, in vitro cell culture, and single-cell RNA sequencing, we show satellite cells communicate with other cells in skeletal muscle during mechanical overload. Early satellite cell EV communication primes the muscle milieu for proper long-term extracellular matrix (ECM) deposition and is sufficient to support sustained hypertrophy in adult mice, even in the absence of fusion to muscle fibers. Satellite cells modulate chemokine gene expression across cell types within the first few days of loading, and EV delivery of miR 206 to fibrogenic cells represses Wisp1 expression …

Saturated Free Fatty Acids Induce Placental Trophoblast Lipoapoptosis, Sathish Kumar Natarajan, Taylor Bruett, Philma Glora Muthuraj, Prakash K. Sahoo, Jillian Power, Justin L. Mott, Corrine Hanson, Ann Anderson-Berry

Department of Nutrition and Health Sciences: Faculty Publications

Obesity during pregnancy increases the risk for maternal complications like gestational diabetes, preeclampsia, and maternal inflammation. Maternal obesity also increases the risk of childhood obesity, intrauterine growth restriction (IUGR) and diabetes to the offspring. Increased circulating free fatty acids (FFAs) in obesity due to adipose tissue lipolysis induces lipoapoptosis to hepatocytes, cholangiocytes, and pancreatic-β-cells. During the third trimester of human pregnancy, there is an increase in maternal lipolysis and release of FFAs into the circulation. It is currently unknown if increased FFAs during gestation as a result of maternal obesity cause placental cell lipoapoptosis. Increased exposure of FFAs during maternal …

Ketogenic Diet As A Preventative Measure Or Treatment Option For Osteoarthritistargeting Nfl Athletes As A High-Risk Group, Kelsi J. Smith

Selected Honors Theses

Osteoarthritis (OA) is a prevalent joint disease that results from the degradation of articular cartilage, leading to inflammation, pain, and eventual joint failure. At one time, it was thought that OA was only the result of the natural decline experienced in old age; however, various risk factors have now been identified that may contribute to an increased risk for developing OA. Risk factors may include joint loading, altered biomechanics, obesity, and joint injury, to which athletes are exposed at a high rate. NFL athletes are one group of athletes that have continued to show a high prevalence of arthritis in …

Purification And Functional Characterization Of The Iron-Responsive Transcription Factor Aft1 From C. Glabrata, Jade Ikahihifo-Bender

Senior Theses

Due to its unique ability to serve as both an electron donor and acceptor, iron is utilized as a co-factor for many biological processes, including electron transfer, oxygen binding, and vitamin synthesis. Iron is also a key factor during fungal infections as the human host and invading pathogens battle over limited iron pools. The primary iron-responsive transcription factor Aft1 in the opportunistic pathogenic yeast Candida glabrata responds to iron deficiency by activating expression of iron acquisition genes. However, the mechanisms for sensing intracellular iron levels and regulating Aft1 activity in response to iron are unknown. The C. glabrata iron regulation …

Intrauterine Transfer Of Polyunsaturated Fatty Acids In Mother–Infant Dyads As Analyzed At Time Of Delivery, Vanessa Woodard, Melissa Thoene, Matthew Van Ormer, Maranda Thompson, Corrine Hanson, Sathish Kumar Natarajan, Maheswari Mukherjee, Ana Yuil-Valdes, Tara M. Nordgren, Arzu Ulu, Kristina Harris Jackson, Ann Anderson-Berry

Department of Nutrition and Health Sciences: Faculty Publications

Polyunsaturated fatty acids (PUFAs) are essential for fetal development, and intrauterine transfer is the only supply of PUFAs to the fetus. The prevailing theory of gestational nutrient transfer is that certain nutrients (including PUFAs) may have prioritized transport across the placenta. Numerous studies have identified correlations between maternal and infant fatty acid concentrations; however, little is known about what role maternal PUFA status may play in differential intrauterine nutrient transfer. Twenty mother–infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood, and placental tissue samples. Plasma concentrations of PUFAs were assessed using gas chromatography (GC‐FID). Intrauterine …

Low Energy Availability With And Without A High-Protein Diet Suppresses Bone Formation And Increases Bone Resorption In Men: A Randomized Controlled Pilot Study, Chaise Murphy, Laura D. Bilek, Karsten Koehler

Department of Nutrition and Health Sciences: Faculty Publications

Suppression of insulin-like growth factor 1 (IGF-1) and leptin secondary to low energy availability (LEA) may contribute to adverse effects on bone health. Whether a high-protein diet attenuates these effects has not been tested. Seven men completed three five-day conditions operationally defined as LEA (15 kcal kg fat-free mass (FFM)^-1 day^-1) with low protein (LEA-LP; 0.8 g protein·kg body weight (BW)^-1), LEA with high protein (LEA-HP; 1.7 g protein·kg BW^-1) and control (CON; 40 kcal·kg FFM^-1·day^-1, 1.7 g protein·kg BW^-1). In all conditions, participants expended 15 kcal·kg …

Immunomodulatory Role Of Urolithin A On Metabolic Diseases, Ashley Mulcahy Toney, Darius Fox, Virginia Chaidez, Amanda E. Ramer-Tait, Soonkyu Chung

Department of Nutrition and Health Sciences: Faculty Publications

Abstract: Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer’s disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms …