Brief Summary of Minutes of Annual Meeting

Annual Meeting Dates: The annual meeting was cancelled due to the COVID-19 pandemic. A tentative meeting will take place in early 2021.

Meeting agenda and minutes

Virtual business meeting to establish the action plan and next year’s agenda. The participants agreed to hold their officer position until next year’s in person meeting.

Ohio State University (Richard Bruno). Background: Green tea extract (GTE), which is rich in polyphenolic catechins, alleviates metabolic endotoxemia and NFkB inflammation to protect against obesity and nonalcoholic fatty liver disease. Activities: Based on established evidence in rodent models, we are actively conducted a randomized placebo-controlled trial to examine GTE to alleviate metabolic endotoxemia by improving gut barrier function in persons with metabolic syndrome. A separate study in rodents is examining dietary supplementation of epigallocatechin (EGCG) vs (+)-catechin (CAT) relative to GTE to ameliorate endotoxemia and nonalcoholic steatohepatitis in mice. Outcomes: Studies in humans are ongoing.  Studies in mice fed a high-fat diet demonstrate that EGCG and CAT similarly protect against endotoxin-TLR4-NFκB inflammation in NASH, but that these catechins exert differential prebiotic and antimicrobial activities. Thus, the catechin-mediated shifts in microbiota composition are unlikely to be entirely responsible for their benefits along the gut-liver axis. In addition, a lack of additive benefit of intact GTE on NASH-associated pathology suggests that catechins are fully responsible for its hepatoprotective activities. Studies in humans are expected to translate these preclinical findings into practical dietary recommendations that help to manage the risk of metabolic disorders driven by TLR4/NFkB inflammation.

University of Arizona (Jennifer Teske). Background: The laboratory focuses on the impact of insufficient sleep on chronic disease and health outcomes. We investigate how sleep curtailment due to environmental noise exposure worsens metabolic health and how the consumption of Western diets exacerbates disease risk during sleep disruption in rodent models. We are also interested in addressing sex differences since women are more sensitive to noise, have a worse sleep and a higher prevalence of obesity compared to men. These studies revealed that females are more vulnerable to the weight-promoting effects of a palatable Western diet and that sleep disruption exacerbates the weight-promoting effects of a palatable Western diet in both males and females. Finally, consumption of Western diets disrupts calorie intake across the estrous cycle, and both sleep disruption and consumption of cafeteria diet reduced estradiol levels. Activities: Conducted analyses to determine the influence of sleep, diet, and sex on micronutrient intake and the role of sex hormones on weight gain in male and females rats. Outcomes: We provided hands-on training and determined proficiency for students at all levels, provided training on anthropometrics, energy expenditure, energy intake, and estrous cycle determination and scientific writing and presentation skills training for both oral and poster presentations for students at all levels.

University of Arizona (Frank Duca). Background: The gut microbiota is a salient contributor to metabolic homeostasis. Obesity is associated with increased consumption of a Western diet, high in fat and sugar, and low in dietary fiber. Increased fiber consumption leads to weight loss, possibly via increased production of short-chain fatty acids (SCFAs), metabolic byproducts of bacterial fermentation of non-digestible carbohydrates. As such, our lab is interested in how SCFAs can improve metabolic homeostasis. Activities: First, we aimed to determine how different diets lead to increased SCFA levels in the intestine and circulation. We performed a fasting-refeeding study in chow, high-fat diet (HFD), and HFD supplemented with 10% prebiotic in rats and collected luminal gut contents and plasma at 0,2,4,6,8 hours post refeeding of an isocaloric meal. Outcomes: We found that chow-fed, but not HFD fed, rats exhibit postprandial rises in SCFA levels in the cecum, which were significantly increased compared to HFD. Supplementation of prebiotics to the HFD partially restored the rise in SCFAs after a meal. However, we found no differences among dietary treatments in the circulation for any of the SCFAs.

University of California Davis (Peng Ji). Background: Our researches use young pigs as a preclinical model and investigate the health benefits and risks of dietary supplements (e.g., micronutrients, plant extracts, and essential oils). One of the research themes aims to determine the metabolic response to and neurological effect of iron deficiency and overload in early development. The prevalence of iron deficiency anemia (IDA) in young children under age 5 is above 40% in many resource-constrained settings but drops below 10% in many developed countries. In contrast to the urgent need of iron treatment, prophylactic iron was commonly given to infants and young children, even those without iron deficiency, through supplements or fortified infant formula and food. Despite extensive research on the consequence of early-life IDA, limited research has evaluated the risk of iron overload in early childhood.

Activity: Two studies were completed during this review period. In study 1, suckling piglets were orally administered different doses of iron supplements to induce IDA, iron repletion (I.R.), and iron overload (I.O.). To assess iron absorption and metabolism, we determined iron content in different tissues/organ where iron is absorbed, stored, utilized, and recycled. Moreover, gene and protein expression of iron regulatory proteins were analyzed in the tissue/organ mentioned above. To assess metabolic response to different iron status, we employed an untargeted metabolomics approach to determine >140 metabolites in plasma and cerebrospinal fluid samples. To evaluate the neurological consequence of early-life IDA and I.O., we performed a behavioral test for sociability and hippocampal-dependent cognition and analyzed the dendritic complexity of hippocampal neurons. In study 2, postweaning piglets were fed diets containing different concentrations of iron to induce IDA, I.R. and I.O., and challenged with enterotoxigenic E. coli that is known to specifically infection pigs. To assess the effects of iron status on resilience to enteric infection and gut microbiota, we determined the severity and duration of diarrhea post-pathogen challenge and performed 16s rRNA sequencing on colon contents and fecal materials.Outcome: The first study led to two papers published in the Journal of Nutrition and several presentations in the American Society of Nutrition Conference and Animal Science conferences. We have been writing manuscripts for the results of study 2. Our other research and collaborative activity also contribute to 3 publications during this review period.

University of California Davis (Yanhong Liu). Background: Recently, a novel concept, non-nutrients, is illuminated to describe a group of dietary compounds that have no nutritional contribution to the animal, but have physiological activities beyond provision of bioavailable nutrients. Those dietary compounds include phytochemicals, prebiotics, probiotics, etc. Emerging evidence suggested that these non-nutrients provided benefits on animal health and production through different modes of action: regulating nutrient digestibility or absorption, and modulating microbial ecology in the digestive tract and/or immune responses. Activities: We were focusing on several probiotics strains on animal health. We have conducted couple of animal trials with pigs to evaluate the effects of probiotics (Bacillus subtilis or Bacillus pumilus) on disease resistance and immunity of weaned pigs that were experimentally infected with a pathogenic E. coli. Outcomes: We observed very positive benefits of supplementing probiotics in animal feed on weaned pig health and performance. In one year of W-4002 support, 1 visiting scientist, 5 graduate students, and several undergraduate students were supervised.

Oregon State University (Emily Ho). Background: Diet plays an essential role in mitigating the development and progression of several cancers, including prostate and breast. This research demonstrates that nutritional strategies that decrease oxidative stress, inflammation, DNA damage and/or target aberrant epigenetic alterations, such as acetylation and methylation, have the potential to dramatically reduce the incidence of cancer. Secondly, declining nutritional status may be a critical determinant of healthy aging and susceptibility to environmental insults.  The research program has focused on bioactive compounds derived from cruciferous vegetables and zinc nutrition. Activities: We have completed a clinical trial investigating the impact of broccoli sprout supplementation in prostate cancer patients.  We have found that supplements are bioavailable and altered expression of AMCR and novel lncRNA. Unlike breast cancer patients, supplementation did not change proliferation markers in prostate. We have also identified additional epigenetic mechanisms involving the acetylation of CCAR2 in chemoprevention of sulforaphane.  We have also employed cell culture models and rodent models to understand the impact of zinc status on exposure to arsenic. We have discovered that zinc deficiency sensitizes the pancreatic islet cells to oxidative stress and altered function.  Outcomes: We have identified new risk factors in prostate and breast cancer and offer novel dietary modifications to reduce the incidence of cancer; Gained knowledge of the mechanisms behind the health benefits of micronutrients and phytochemicals such as zinc and compounds derived from cruciferous vegetables; Established low dietary zinc as a risk factor for inflammatory processes, DNA damage and cancer risk and identify new biomarkers for human zinc deficiency;  Established function of zinc and changes in zinc metabolism with toxicological stresses, development, and aging.

Oregon State University (Norman Hord). Background: Dietary nitrate supplementation improves exercise performance by reducing the oxygen cost of exercise, increasing exercise tolerance, and metabolic efficiency. However, the mechanisms for these performance effects in skeletal muscle is not well understood. Dietary exposure to nitrates and nitrites occurs mainly from vegetable sources. This exposure is associated with cardiovascular health benefits and improved athletic performance while, in the context of processed meats consumption, is associated with increased gastrointestinal cancer risk. Dietary nitrite and nitrate can act as reservoirs for nitric oxide (NO) production with its reduction to NO potentiated in acidic or hypoxic areas, such as contracting skeletal muscle. We used dietary nitrate and nitrite in a zebrafish model to show that dietary nitrate improves exercise performance by lowering the oxygen cost of physical activity. Activities: This project addresses two W4002 project objectives related to the metabolism and efficacy of dietary nitrate to improve the performance of zebrafish during endurance exercise. We utilize untargeted (LC/MS-MS) metabolomics and targeted (¹H-NMR) spectroscopic methods to interrogate nitrate-dependent changes in metabolic fuels in the whole zebrafish and zebrafish muscle, brain, and liver at rest and during endurance exercise. Outcomes: Building on performance improvement data in whole zebrafish due to nitrate treatment, we now show that nitrate treatment significantly increased skeletal muscle nitrate concentrations 2.5-fold at baseline and exercise significantly decreased muscle concentrations in nitrate-treated to levels found in control, untreated skeletal muscle. As expected, nitrate exposure decreased the oxygen cost of exercise during an endurance protocol. Metabolomics data revealed an increase in phosphocreatine (PCr), creatine (Cr), adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), glycolytic, fatty acid and tricarboxylic acid cycle (TCA) intermediates in nitrate-treated skeletal muscle at rest and a concomitant decrease after peak exercise. Notably, exercise did not change or increased; these metabolites in control skeletal muscle. We conclude that nitrate may improve performance by increasing the availability of metabolic fuels (ATP, NAD, glycolytic and TCA intermediates, PCr, lactate, pyruvate, acyl carnitines and phospholipids) in rested zebrafish skeletal muscle.

Oregon State University (David Dallas). Background: Our lab examines the digestion of milk protein and the release of bioactive peptides in infants and adults. Activities: This year, we have examined the survival of bioactive peptides across the mammary gland to the infant's stomach, intestine, and stool and published on most of these. We have demonstrated that these peptides have antimicrobial and immunomodulatory actions. We have also conducted human trials where bioactive proteins, casein glycomacropeptide, was fed to adult subjects, and intestinal samples were collected. Using mass spectrometry-based glycopeptidomics, we demonstrated that some glycomacropeptide survives intact to the intestine, but most are in the form of glycopeptide fragments of the original. We have demonstrated that glycomacropeptide has immunomodulatory actions in vitro. We are designing a clinical trial to test the effect of GMP on the adult gut microbiota and the immune system. We also examined the digestion of human milk and recombinant antibodies in preterm infants and determined the extent to which they survive. This project was performed to inform the design of future antibody-based therapies in infants. Outcomes: We identified thousands of milk peptides in the infant's stomach, intestine, and stool, many of which are bioactive. We identified bioactive fractions of these. We demonstrated the extent to which antibodies survive in infants and bioactive peptides survive in the adult digestive tract.

University of Illinois – Urbana-Champaign (Jaume Amengual). Background: β-carotene is the primary precursor of vitamin A in mammals, and a potent antioxidant in lipid-rich environments. My laboratory focuses on understanding the role of β-carotene in obesity and atherosclerosis, two diseases deeply related to lipid metabolism. Activities: This past year, my laboratory was focused on elucidating the mechanism(s) by which β-carotene reduces cholesterol and triglyceride plasma concentrations. Using a mouse model lacking the enzyme involved in the conversion of β-carotene to vitamin A (β-carotene oxygenase 1, BCO1), we study the bioactive properties of intact β-carotene and its derivatives (vitamin A and retinoic acid). The positive effects of β-carotene and retinoic acid on plasma lipid concentrations were clinically evaluated by using a low-density lipoprotein receptor (LDLR) deficient mice (Ldlr^-/- mice). By combining Ldlr^-/- mice and Bco1^-/- mice, we have successfully generated a humanized mouse model in which β-carotene accumulates in tissues, plasma, and atherosclerotic lesions. Outcomes: The characterization of this mouse model is currently under preparation.

University of Illinois – Urbana-Champaign (Juan Andrade). Background: Our laboratory is focused on the design and optimization of novel delivery routes of micronutrients, and the development of cutting-edge tools to detect micronutrients in foods. Activities: Project 1: Characterization of legume-based protein nanoparticles. Nanoaggregates based on pea protein isolate containing vitamin D were characterized in terms of stability and bioavailability in an animal model of vitamin D deficiency. We found that the dispersion of vitamin D in nanoaggregates enhances its oral bioavailability and bioefficacy. Project 2: Low-cost micronutrient sensors. We have created a paper-based, smartphone-assisted assay for the inexpensive determination of iron in fortified flours. Outcomes: This technology can be used to assert the quality of fortified flours by companies as well as monitoring their compliance by government inspectors in low-income settings.

Kansas State University (Brian Lindshield). Background: Our laboratory designs and experiment on fortified food products to analyze their potential in the promotion of health and prevention of disease. Activities and Outcomes: We completed the analysis and write up of results from rat fortified blended foods and fortified rice studies. We plan to submit our results for publication in the near future. We plan to do a follow-up study with the rice before submitting a combined manuscript for both for publication. We have plans in place for a study to determine whether saliva can be used to assess iron bioavailability and status as a less invasive measure than blood.

Montana State University (David Sands). Background: Crop plants are generally selected by plant breeders for the yield-limiting traits, including disease and insect resistance. Nutritional traits are seldom considered. Activities and Outcomes: In the past decade we have succeeded in developing high lysine spring wheat (3 cultivars), high lysine tomatoes (3 cultivars), high protein/low glycemic oats (Proatina-commercialized), low glycemic peas (commercialized), low glycemic potatoes 6 cultivars) and Camelina sativa microgreens (high omega-3 line currently on a space flight. Development of nutritious lines of crops is easily done if plant breeders are aware of the breeder’s dilemma (yield versus nutrition) and if they are given selection tools that are easily adapted to high throughput screening. The traits that we targeted included high lysine that can be assayed by lysine knockout mutants of E. coli. Low glycemic traits can be assayed by observation of starch granule structure revealing high amylose: low amylopectin ratios. High protein oats were assayed using NIR spectroscopy. These oats are one source of plant sourced protein in high demand. Three manuscripts and several patents are in preparation.

Oklahoma State University (Dingbo Lin). Background: Carotenoids are a large group of lipophilic pigments. Dietary ingestion is the only source of carotenoids for human nutrition and health. My laboratory focuses on the health benefits of carotenoids and the metabolic enzymes in the prevention of obesity, diabetes, and influenza virus infection. Activities: We used mouse models to determine: 1) astaxanthin alteration of gut microbiome in the wild type and beta-carotene oxygenase 2 (BCO2) knockout mice; 2) BCO2 as a protein in mitochondrial function; and 3) wheat germs in improving gut microbiome homeostasis in mice. Outcomes: We identified the specific profiles of gut microbiome in response to astaxanthin and wheat germs. We also characterized that BCO2 expression levels significantly impacted retinal mitochondrial morphology and function. The Deletion of BCO2 caused low-grade inflammation and elevation of blood glucose.

University of Rhode Island (Brietta Oaks). Background: Lead exposure is a major public health concern in Rhode Island. There is evidence that omega-3 fatty acid intake may reduce circulating lead concentrations, but research has been limited and has not been explored in pregnant women, whom are at a higher risk for adverse effects of lead exposure. In addition, omega-3 fatty acid intake may reduce circulating cortisol, a stress hormone, which has negative effects during pregnancy if at chronically high concentrations. Activities: This research project did not get funded during this timeframe, so time was spent conducting literature reviews and writing a new grant to the Rhode Island Foundation. Outcomes: We received the grant from the Rhode Island foundation and will begin data collection as soon as regulations around research during COVID-19 allow research activity.

Purdue University (Lavanya Reddivari). Background: Determine the efficacy and mechanisms of action of nutrients and dietary bioactive compounds towards improved health. Inflammatory bowel disease (IBD) diminishes the quality of life as well as promotes risk for colon cancer. There is a growing interest in safe and effective preventive strategies against IBD. Naturally occurring flavonoid compounds are promising preventive and therapeutic candidates against IBD due to their poor bioavailability leading to greater levels in the intestine and their ability to modulate immune signaling mediators in the gut. Activities: We used different genotypes of maize and potato to investigate the anti-inflammatory properties of flavan-4-ols and anthocyanins (two types of flavonoids) in mice models of colonic inflammation. Supplementation with maize kernels containing flavan-4-ols (red kernels) and potatoes containing anthocyanins (red and purple tubers) suppressed the relative expression of several chronic inflammatory markers. Gut permeability, an important marker of colitis, was also suppressed in animals consuming flavonoid-containing diets. Outcomes: These results suggest the protective effect of flavan-4-ols and anthocyanins and provide a rationale to optimize genotypes and processing conditions to improve phytonutrient content for better dietary benefits.

University of Maine (Dorothy Klimis-Zacas). Background: With the aging population and the increase in obesity and diabetes worldwide, health care professionals predict an increase in ulcers and chronic wounds.  Additionally, pressure ulcers present in many patients with chronic diseases, as well as conditions associated with burns and the need for tissue regeneration and repair, involve balanced wound healing. Unbalanced wound healing and tissue repair can lead to severe outcomes such as septicemia, which comes with high mortality rates. At the present time, there are no effective treatments to speed up wound healing and improve tissue remodeling. Thus, there is a need to develop effective, new cost-effective therapies that have no deleterious side effects and enable patients to recover faster and improve the quality of their lives.  Our results from previous years documented a differential response of wild blueberry extracts on endothelial cell migration and relevant proteins and their gene expression, based on type of fraction and its concentration. Studies on angiogenesis also documented a concentration-depended effect, critical concentrations at which angiogenesis is modulated and differential response based on the different fractions (ACNs, anthocyanins or Phen, phenolic acids). ACNs seem to inhibit HUVEC migration and angiogenesis while P.A.s promote this process.  Thus, the goal of the present project is to investigate anthocyanin (ACNs) and phenolic acid (Phen) fractions and their combination extracted from wild blueberry powder on wound healing and angiogenesis in an animal model. The objectives of this project are to 1) validate our in vitro results with an in vivo model and 2) design a prototype (patch or spray) embedded with phenolic acids of a specific concentration. This patch or spray will be designed to be applied quickly and easily in any type of wound injury, providing anti-inflammatory and antimicrobial protection, as well as faster tissue repair and prevention of tissue fibrosis. Activities: During the first year of this project, I formed a team to aid in the development of a biomedical prototype for wound healing and conduct customer discovery and market analysis. From the above experience, we have been able to shape our approach for our in vivo, a preclinical research study that began September 2019, and the development and commercialization of our product to meet the specific needs of stakeholders. The preclinical study was completed, and data are presently analyzed.  Endpoints under study are speed of wound healing, protein activity and gene expression of several proteins responsible for inflammation, angiogenesis and tissue regeneration.  Another project initiated in 2017 and was completed in 2019, targeted the role of Red Raspberries (Rubus idaeus) on endothelial function (vasoconstriction and vasodilation) and obesity-induced inflammation by assessing pro-inflammatory markers and their gene expression in hepatic and adipose tissues in an animal model of the Metabolic Syndrome (MetS), the Obese Zucker Rat (OZR). Preliminary results support the role of Red Raspberries in normalizing the endothelial dysfunction and attenuating inflammation associated with MetS. Manuscripts are under review.

Outcomes: Results from the period covered were disseminated in the form of posters and oral presentations at the biannual Health Benefits Symposium in Portland, and as oral presentations at the American Society for Nutrition, Baltimore. Additionally, T.V. interviews were given, and newspaper articles were published on the projects described above.

University of Missouri (Ingolf Gruen). Background: One of the key elements affecting bioavailability and bioactivity of nutrients is the food matrix that they are in. Thus, the analysis of the concentration of volatile and non-volatile (phyto-) nutrients, and the estimation of their release from the food matrix is directly related to their potential bioavailability and bioactivity. Chocolate is made from the fermented, dried, and roasted seeds of the Theobroma cacao tree. It is now understood that cacao, contains a variety of compounds, including well-known flavonoid polyphenols, the consumption of which has positive impacts on human heart health and blood pressure, cancer reduction, LDL cholesterol reduction, and insulin resistance improvements, as numerous in vitro, in vivo, and observational studies have confirmed. However, there is an unwillingness by many Americans to consume higher-cacao-content chocolate, which is more bitter. Therefore, if the bitterness of cacao could be minimized, higher-cacao-content and lower-sugar chocolate confection sales could capture an even larger segment of the conventional and healthy snack-food market by achieving the elusive combination of being both tasty and healthy. Activities:  We produced three 70% dark chocolates differing only in their roast profile (raw, generic medium roast, generic dark roast), and had 126 chocolate consumers rate Overall Liking, perceived sweetness, and perceived bitterness on 9-point scales.

Outcomes: Analysis of variance (ANOVA) showed significant differences (p<0.05) in the chocolates for all three characteristics. Significantly lower bitterness and higher liking were seen for both of the roasted chocolates, with the Medium-Roast having the lowest bitterness and highest liking rating (p<0.05). Roasting also significantly increased the sweetness of the chocolates (p<0.05). Differences in bitterness and liking ratings between 70% dark chocolate made from raw and roasted cacao were quite striking. Specifically, we found a 21% reduction in bitterness between the Raw and the Medium-Roast chocolate, which is also correlated with a 27% increase in liking for the Medium-Roast chocolate. Furthermore, bitterness was 8% lower, and liking was 10% higher for the Medium-Roast chocolate compared to the Dark-Roast chocolate.

University of Nebraska-Lincoln (Janos Zempleni). Background: Virtually every cell produces and secretes exosomes (nanoparticles) loaded with cargos such as various species of RNAs, proteins, and lipids. Exosomes play essential roles in cell-to-cell communication. The transfer of exosomes cargos from donor cells to receptor cells alters gene expression and metabolism in receptor cells. Activities: We have made the paradigm-shifting discovery that exosomes and their cargos do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as bovine milk and chicken eggs. Outcomes: 1) We have show that milk exosomes alter the gut microbiome. 2) We have shown that milk exosomes do not elicit an immune response if administered orally to mice or added to cultures of human peripheral blood mononuclear cells ex vivo. This is an important observation, because milk exosomes are candidates for delivering chemotherapeutics to brain cancer patients. 3) We have identified glycans on the surface of milk exosomes essential for exosome absorption by mucosal cells in the G.I. tract. 4) We have shown that milk exosomes carry microbial mRNAs, and that the mRNAs are bioavailable in humans and increase the survival of an influenza A. challenge in mice. 5) We have shown that dietary depletion of milk exosomes causes a loss of fecundity due to loss of oocyte implantation and embryo adhesion. 6) We have shown that maternal knockout of exosome and microRNA biogenesis impairs growth and G.I. health in wild-type pups fostered to the dams. 7) We have shown that milk exosomes select for polymorphisms and mutations in gut microbiome cultures, and exosome-free media selects for mutations in gut pathogens that increases virulence 8) We have shown that milk exosomes and their microRNA cargos are bioavailable and accumulate primarily in the G.I. mucosa, liver and brain.

University of Connecticut (Ji-Young Lee). Background: Liver fibrosis, characterized by excessive accumulation of extracellular matrix, results from the dysregulated wound-healing response in the liver caused by alcohol, chronic hepatitis, viral infection, immune system imbalance, and obesity-related disorders. The activation of hepatic stellate cells (HSCs) is an essential event in the development of liver fibrosis. Quiescent HSCs (qHSCs) are transdifferentiated into myofibroblast-like cells (i.e., activated HSCs (aHSCs) in the injured liver, which have high expression of α smooth muscle actin (αSMA), a myofibroblast marker, and produce ECM proteins such as procollagen type I α1 (COL1A1). Fucoxanthin (FCX), a xanthophyll carotenoid, is abundant in edible brown seaweeds. Studies have demonstrated that FCX exerts antioxidant, anti-inflammatory, neuroprotective, and anti-proliferative effects. However, whether FCX has anti-fibrogenic properties in HSCs has never been determined. Activities: We evaluated the effect of FCX on fibrogenesis in LX-2 cells, a human HSC cell line, as well as primary human and mouse HSCs to gain insight into its potential role in the development of liver fibrosis. Outcomes: FCX significantly decreased basal and transforming growth factor β1 (TGFβ1)-induced mRNA levels of fibrogenic genes with concomitant decreases in their protein levels in LX-2 cells. The phosphorylation of SMA- and MAD-related protein (SMAD3) was increased by TGFβ1, which was attenuated by FCX. Importantly, when LX-2 cells were treated with FCX and SIS3, a SMAD3 inhibitor, there was synergistic repression of fibrogenic gene expression. The anti-fibrogenic effect of FCX was also confirmed in primary human HSCs. FCX prevented TGFβ1-induced accumulation of reactive oxygen species by diminishing mRNA level of NADPH oxidase 4 (NOX4) in LX-2 cells. When FCX was present during the activation of quiescent mouse primary HSCs, it decreased the expression of fibrogenic genes while diminishing intracellular lipid droplets. The results suggest that FCX exerts an anti-fibrogenic effect in HSCs primarily by preventing TGFβ1-induced pro-fibrogenic genes expression via inhibition of SMAD3 activation and by inhibiting the activation of quiescent HSCs.

The University of Hawaii at Manoa (Kacie KHY Ho). Background: Many agricultural commodities are known to be rich sources of nutrients, vitamins, minerals, and bioactive phytochemicals (e.g., polyphenols, carotenoids), all of which may provide beneficial health effects. However, health impacts and bioactivity of many phytochemicals are limited by bioaccessibility, i.e., the relative amount of phytochemical that is stable against digestion and available to be absorbed in the small intestines. The technical goals of this research proposal are to identify and quantify the major nutrients and phytochemicals (and their potential interactions) in post-harvest commodities across different varieties and to elucidate the effect of the food matrix on bioaccessibility. Gaining a better understanding of phytochemical bioaccessibility, namely the effects of plant variety and processing on bioaccessibility, will help to optimally deliver benefits from available crops for the local consumer or to add-value to exported products. Activities: Bioactive phytochemicals will be extracted from agricultural commodities (e.g., raw fruit vs. processed fruit). Bioaccessibility will be measured by subjecting samples to simulated digestion to estimate the relative amount that is stable against digestion and available for absorption. Data/results will provide information on if certain types of processing or varieties of agricultural products or to provide improved bioaccessibility of bioactive phytochemicals compared to others. So far, work has been completed for papaya (Carica papaya) to compare carotenoid content and bioaccessibility across cultivars. Work on Hawaiian taro (Colocasia esculenta) has been initiated to determine the effect of thermal processing on carotenoid and polyphenol bioaccessibility across 4 different cultivars (results still pending). Outcomes: Research was completed to compare carotenoid content and bioaccessibility from different papaya (Carica papaya) cultivars (Laie gold, Rainbow, Kapoho Solo, Sunrise, and Sunset). Similar to previous research, our findings indicated that differences in carotenoid content existed across different cultivars, with all tested cultivars containing significant amounts of beta-carotene and beta-cryptoxanthin. Two cultivars were red-fleshed and contained lycopene (~1089-1570 μg/100g). Beta-carotene and beta-cryptoxanthin bioaccessibility were significantly greater in Rainbow cultivars compared to others. Lycopene bioaccessibility was significantly higher for Sunrise, a GMO red-fleshed cultivar, compared to Sunset, a non-GMO red-fleshed cultivar. Overall, the findings suggest that significant differences in both carotenoid content and bioaccessibility can exist depending on the cultivar. This work was accepted for presentation at the 2020 American Oil Chemists’ Society Meeting

1. MG Traber, GR Buettner, RS Bruno. (2019). The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome. Redox Biology (Invited Review), 21:101091. doi: 10.1016/j.redox.2018.101091
2. I Hatsu, C Gunther, E Hade, S Vandergriff, N Slesnick, R Williams, R Bruno, J Kennel. (2019). Unaccompanied homeless youth have extremely poor diet quality and nutritional status. Int J Adol Youth, 24:3, 319-332. doi: 10.1080/02673843.2018.1538885
3. P Dey, GY Sasaki, P Wei, L Wang, J Li, C Chitchumroonchokchai, J Zhu, D McTigue, Z Yu, RS Bruno. (2019). Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation. J Nutr Biochem, 67:78-89.
4. LE Griffin, DW Fausnacht, JL Tuzo, AK Addington, KC Racine, H Zhang, MD Hughes, KM England, RS Bruno, SF O’Keefe, AP Neilson, AC Stewart. (2019). Flavanol supplementation protects against obesity-associated increases in systemic IL-6 levels without inhibiting body mass gain in mice fed a high-fat diet. Nutr Res, 66:32-47.
5. R Williams, A Rose, RS Bruno, A Hanks, J Kennel, J McDonald, C Gunther. (2019). Examination of the relationship of diet quality with cardiometabolic risk factors in apparently healthy college students. J Am Coll Health, 8:148. doi: 10.4103/jehp.jehp_12_19.
6. P Dey, JB Kim, C Chitchumroonchokchai, J Li, GY Sasaki, BD Olmstead, KL Stock, JM Thomas-Ahner, SK Clinton, RS Bruno. (2019). Green tea extract inhibits early oncogenic responses in mice with nonalcoholic steatohepatitis. Food Funct, 10, 6351-6361.
7. GY Sasaki, J Li, MJ Cichon, KM Riedl, RE Kopec, RS Bruno. (2019). Green tea extract treatment in obese mice with nonalcoholic steatohepatitis restores the hepatic metabolome in association with limiting endotoxemia-TLR4-NFkB-mediated inflammation. Mol Nutr Food Res, 63(24):e1900811. doi: 10.1002/mnfr.201900811.
8. BK Alba, AE Stanhewicz, P Dey, RS Bruno, WL Kenney, LM Alexander. (2020). Controlled feeding of an 8-day high dairy cheese diet prevents sodium-induced endothelial dysfunction in the cutaneous microcirculation through reductions in superoxide. J Nutr, 150(1):55-63; doi: 10.1093/jn/nxz205.
9. KM Hirahatake, RS Bruno, BW Bolling, C Blesso, LM Alexander, SH Adams. (2019). Dairy foods and dairy fats: new perspectives on pathways implicated in cardiometabolic health. Adv Nutr, 11(2):266-279. doi: 10.1093/advances/nmz105.
10. KM Ranard, MJ Kuchan, RS Bruno, JM Juraska, JW Erdman. (2020). Synthetic α-tocopherol, compared with natural α-tocopherol, downregulates myelin genes in cerebella of adolescent Ttpa-null mice. J Nutr, 150(5):1031-1040. doi: 10.1093/jn/nxz330.
11. JK Hodges, J Zhu, Z Yu, Y Vodovotz, G Brock, GY Sasaki, P Dey, RS Bruno. (2020) Intestinal-level anti-inflammatory bioactivities of catechin-rich green tea: Rationale, design, and methods of a double-blind, randomized, placebo-controlled crossover trial in metabolic syndrome and healthy adults. Contemp Clin Trials Commun. 17:100495. doi: 10.1016/j.conctc.2019.100495
12. MM Kemski, CA Rappleye, K Dabrowski, RS Bruno, M Wick. (2020). Transcriptomic response to soybean meal-based diets as the first formulated feed in juvenile yellow perch (Perca flavescens). Sci Rep, 10(1):3998. doi: 10.1038/s41598-020-59691-z.
13. Coborn JE, Lessie RE, Rance NE, Sinton CM, Perez-Leighton CE, Teske JA. Noise-induced sleep disruption increases weight gain and decreases energy metabolism is female rats. 2019. Int J Obes (Lond). 43(9):1759-1768.
14. Waise TM, Rasti M, Duca FA, Zhang SY, Bauer PV, Rhodes CJ, Lam TK. Inhibition of Upper Small Intestinal mTOR Lowers Plasma Glucose Levels by Inhibiting Glucose Production. Nat Commun 2019, 10(1):704.
15. Ji P, Lönnerdal B, Kim K, Jinno CN. Iron Oversupplementation Causes Hippocampal Iron Overloading and Impairs Social Novelty Recognition in Nursing Piglets. J Nutr. 2019, 149(3):398-405.
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