Molecular, Genetic, and Biochemical Nutrition Commons^™

Γ-Glutamyl Valine, Found In Dry Edible Beans, Is Anti-Diabetic In Db/Db Mice, Bikram Upadhyaya, Kaustav Majumder, Regis Moreau

Nutrition and Health Sciences -- Faculty Publications

Objectives: Dietary γ -glutamyl peptides (γ -GPs) found in dry edible beans exhibit biological activities (antioxidant, anti-inflammatory) with potential benefits against chronic metabolic disorders. γ -GPs are responsible for the desirable Kokumi flavor through allosteric activation of the Calcium Sensing Receptor (CaSR) present in multiple mammalian tissues. In this study, we investigated the metabolic effects of γ -glutamyl valine (γ -EV) in diabetic obese mice.

Conclusions: γ -EV improved the diabetic condition of db/db mice via modulation of glucose and lipid metabolism.

Practices Of Vitamin D Supplementation Leading To Vitamin D Toxicity: Experience From A Low-Middle Income Country, Siraj Muneer, Imran Siddiqui, Hafsa Majid, Nawazish Zehra, Lena Jafri, Aysha Habib

Department of Pathology and Laboratory Medicine

Introduction: The trend of prescribing VD preparations for nonspecific body aches and self-medication has increased significantly. The importance of vitamin D toxicity (VDT) has been underestimated and under recognized. This study was done to determine the frequency toxicity (>150 ng/ml) in subjects for 25-hydroxyvitamin D (25OHD) and evaluate the vitamin D (VD) supplements used by these subjects.
Methodology: This descriptive cross-sectional study was conducted at the Section of Chemical Pathology, Aga Khan University Hospital Karachi from April 2020 to March 2021. Subjects with 25OHD toxicity were contacted and information related to history of calcium and VD supplementation were collected. …

Mechanical Overload-Induced Muscle-Derived Extracellular Vesicles Promote Adipose Tissue Lipolysis, Ivan J. Vechetti Jr, Bailey D. Peck, Yuan Wen, R Grace Walton, Taylor R. Valentino, Alexander P. Alimov, Cory M. Dungan, Douglas W. Van Pelt, Ferdinand Von Walden, Bjorn Alkner, Charlotte A. Peterson, John J. Mccarthy

Nutrition and Health Sciences -- Faculty Publications

How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle-specific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2α, a known repressor of Adrβ3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of …

The Studies Of Effects Of Vitamin A Status On Type 2 Diabetes In Zucker Diabetic Fatty Rats And Retinoic Acid On Glucose Transporter 4 Expression In L6 Cells, Tiannan Wang

Doctoral Dissertations

The epidemic of metabolic diseases such as diabetes has become a public health concern. Previous research data from our lab have shown that vitamin A (VA) status and retinoic acid (RA), a metabolite of VA, contribute to the glucose and lipid metabolism in the body and cells. As the skeletal muscle contributes to metabolic homeostasis, the effects of VA signaling system on its glucose metabolism are worth to be investigated. Here in this dissertation, the following two projects were carried out to study the VA’s role in the control of metabolism. (1) The effects of VA status on the development …

Effects Of N-3 Pufa-Derived Epoxides Combined With Seh Inhibition On Brown Adipose Tissue And Brown Adipocytes In Obesity, Yang Yang

Doctoral Dissertations

Brown adipose tissue (BAT) has become a promising target for obesity treatment and prevention. However, effective dietary factors to promote BAT mass and function have not been identified. 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are two prominent epoxy fatty acids (EpFAs) produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. EpFAs are quickly metabolized to less active diols by soluble epoxide hydrolase (sEH). In this dissertation, the effects of an sEH inhibitor (t-TUCB) (which stabilizes EpFAs) alone or combined with n-3 EpFAs on thermogenic activity in the BAT and brown adipocytes in …

Investigating Therapeutic Strategies To Target Metabolic Vulnerabilities Of Nsclc Tumors With Mutant Keap1 Gene, Pranavi Koppula

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The metabolic vulnerability of cancers has long been envisaged as an attractive window to develop novel therapeutic strategies. Metabolic flexibility at the cellular level encompasses the efficient rerouting of anabolic and catabolic pathways in response to varying environmental stimuli to maintain cellular homeostasis and sustain proliferation. The primary objective of this study is to identify metabolic vulnerabilities bestowed by KEAP1/NRF2 signaling axis through SLC7A11. SLC7A11 is a transcriptional target of NRF2, an essential regulator of cellular anti-oxidant response. Under unstressed basal conditions, NRF2 interacts with KEAP1, a tumor suppressor gene and a substrate adaptor protein of the Cullin3-dependent ubiquitin ligase …

Evidence Of Myomir Regulation Of The Pentose Phosphate Pathway During Mechanical Load-Induced Hypertrophy, Taylor Valentino, Vandre C. Figueiredo, C. Brooks Mobley, John J. Mccarthy, Ivan Jose Vechetti Jr

Nutrition and Health Sciences -- Faculty Publications

Many of the molecular and cellular mechanisms discovered to regulate skeletal muscle hypertrophy were first identified using the rodent synergist ablation model. This model reveals the intrinsic capability and necessary pathways of skeletal muscle growth in response to mechanical overload (MOV). Reminiscent of the rapid cellular growth observed with cancer, we hypothesized that in response to MOV, skeletal muscle would undergo metabolic programming to sustain increased demands to support hypertrophy. To test this hypothesis, we analyzed the gene expression of specific metabolic pathways taken from transcriptomic microarray data of a MOV time course. We found an upregulation of genes involved …

Qupath Digital Immunohistochemical Analysis Of Placental Tissue, Ashley L. Hein, Maheswari Mukherjee, Geoffrey A. Talmon, Sathish Kumar Natarajan, Tara M. Nordgren, Elizabeth Lyden, Corrine K. Hanson, Jesse L. Cox, Annelisse Santiago‑Pintado, Mariam A. Molani, Matthew Van Ormer, Maranda Thompson, Melissa K. Thoene, Aunum Akhter, Ann Anderson‑Berry, Ana G. Yuil-Valdes

Nutrition and Health Sciences -- Faculty Publications

Background: QuPath is an open‑source digital image analyzer notable for its user‑friendly design, cross‑platform compatibility, and customizable functionality. Since it was first released in 2016, at least 624 publications have reported its use, and it has been applied in a wide spectrum of settings. However, there are currently limited reports of its use in placental tissue. Here, we present the use of QuPath to quantify staining of G‑protein coupled receptor 18 (GPR18), the receptor for the pro‑resolving lipid mediator Resolvin D2, in placental tissue. Methods: Whole slide images of vascular smooth muscle (VSM) and extravillous trophoblast (EVT) cells stained …

Exercise Is Medicine: Health And Fitness At The U Of A And Beyond, Erin Howie Hickey

Seminars

Dr. Howie Hickey will discuss the latest research on the benefits of physical activity for physical and mental health, from COVID-19 to depression, including what the science can say about the optimal dose and intensity. She will share recent data collected by the Exercise is Medicine team on physical activity, fitness and wellness in the University of Arkansas community and discuss future directions and opportunities.

The Importance Of Exercise And Nutrition In Early Life, Elisabet Borsheim

Seminars

Dr. Børsheim will present her research on the important of exercise and nutrition in early life. In her presentation Dr. Børsheim will focus on childhood obesity and show that this can increase risk for later life metabolic dysfunction. She will discuss if physical fitness can attenuate negative effects of obesity in children and if there are critical windows of development where physical activity is of specific importance. Finally, she will present data on impact on early physical activity and nutrition on response to exercise later in life.

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

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

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

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 …

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

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

Nutrition & Health Sciences Dissertations & Theses

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

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 J. Johnson

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 …

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

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

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 …