Research Project: Improving Public Health by Understanding Metabolic and Bio-Behavioral Effects of Following Recommendations in the Dietary Guidelines for Americans

Location: Obesity and Metabolism Research

2021 Annual Report

Objectives
The following research project addresses a key unmet need of the USDA Human Nutrition Program, namely to test the metabolic impact of the Dietary Guidelines for Americans (DGA) --which has immediate nutrition policy implications. To achieve this goal, project scientists have designed an interdisciplinary effort leveraging tools from analytical chemistry, biochemistry, clinical nutrition, endocrinology, exercise biology, genetics, molecular biology, physiology, and psychological/CNS-based assessments - applying cutting edge phenotyping tools alongside complementary basic research experiments. Objective 1: Determine if achieving and maintaining a healthy body weight is the key health promoting recommendation of the Dietary Guidelines for Americans (DGA). Sub-objective 1A: Determine if achieving and maintaining a healthy body weight improves cardiometabolic risk in persons at-risk for metabolic disease. Sub-objective 1B: Determine if chronic stress, stress system responsiveness, and diet quality interact to influence metabolic responses and if these responses can be sustained over time. Sub-objective 1C: Determine the eating behavior characteristics, including dietary restraint, food cravings and preferences, motivation for food choice, and satiety response to a meal challenge to evaluate a) how diet interventions affect these variables b) which behavioral variables are associated with adherence to prescribed diet during the fully controlled interventions (mos 1 & 2) and during the partially controlled interventions (mos 3-6) c) and body weight changes during the follow-up period. Sub-objective 1D: Determine how weight loss and diet interact to influence lipoprotein particle metabolomic structure and their association with cardiometabolic risk factors. Objective 2: Identify hepatic gene polymorphisms associated with metabolic response to diets. This objective complements and integrates with Objective 1, which systematically tests the effect of the DGA. Objective 2 studies are designed to identify genetic sources of variation and their impact on metabolism in response to diet using a population of mice with defined genetic diversity to answer the following sub-objectives: Sub-objective 2A: Identify gene-diet interactions affecting adiposity and hepatic fat accumulation. Sub-objective 2B: Identify changes in gut microbiome composition associated with resistance to weight loss. Sub-objective 2C: Determine how atherogenic risk mechanisms alter lipoprotein particle lipidomic structure in cardiometabolic disease models. Objective 3: Develop Reference Values for mineral and vitamin concentrations in human milk, which will improve estimates of recommended nutrient intakes for breastfeeding infants and their mothers.

Approach
Objective 1 Hypotheses: 1A1: Consuming a DGA diet pattern for 8 wk will improve cardiometabolic risk factors, primarily insulin sensitivity and lipid profiles, compared to a typical American diet (TAD); 1A2: Cardiometabolic improvements resulting from the DGA diet will be greater in overweight/obese women when energy intake is restricted to result in weight loss; 1B: Phenotypic differences in psychological stress will partly explain variation in metabolic responses to a healthy diet; 1C1: Hunger, circulating ghrelin, and snack selection following a meal challenge will be greater with energy-restricted diets; 1C2: Adherence to the DGA diets will be better than adherence to the TAD diets when controlled for eating behavior, cognitive function, and subjective satiety; 1C3: Body weight changes in the follow-up period will associate with endocannabinoid tone, craving, and increased palatable food intake independent of intervention group; 1D1: Weight loss-induced metabolomic changes in plasma particles will decrease LDL region pro-atherogenic character, while increasing HDL anti-atherogenic character; 1D2: Diets rich in fruits, vegetables, and omega-3 fatty acids will reduce the 8 wk concentrations of non-enzymatically generated oxygenated lipids in LDL region lipoproteins. Objective 2 Hypotheses: 2A: Reduction in adiposity associated with dietary change is due to both genetic and dietary interactions; 2B: Gut microbial diversity will affect the weight loss response in a genetically diverse mouse population; 2C: Dietary manipulations will differentially change the lipoprotein oxylipins and ceramide composition in atherosclerosis prone vs. resistant cardiometabolic disease mouse models. A Randomized Control Trial will address hypotheses under Objective 1. This trial will be an intervention with human volunteers randomized to one of four parallel diet groups: 1. participants will consume a diet based on the Dietary Guidelines for Americans (DGA) and maintain energy balance; 2. participants will consume a control diet based on the typical American diet (TAD) and maintain energy balance; 3. participants will consume a DGA diet, restricted in calories to stimulate body weight loss; and 4. participants will consume a TAD, restricted in calories in order to stimulate body weight loss. A complementary mouse experiment will address Objective 2 hypotheses. This study will use diets formulated to match the diet types used in Objective 1 for the TAD and DGA. Four experimental groups will be tested: Ad libitum DGA diet; energy restricted DGA diet; ad libitum TAD diet; and energy restricted TAD diet. This study utilizes a systems genetic approach using genetic reference panels to assess gene x diet interactions that affect both the susceptibility to obesity and the resistance to weight loss. Objective 3 Hypothesis: Reference Values for vitamins and minerals in human milk can be established by measuring the range of concentrations in milk from well-nourished women who are not consuming additional micronutrients through supplements or fortified foods.

Progress Report
Under Objective 1, ARS researchers in Davis, California, designed and began conducting a pilot study to test the usability of continuous glucose monitors and physical activity monitors, which are research instruments and wearable devices to be used in the Objective 1 human intervention study. To support the Objective 1 human intervention study, a Physiologist was hired in July 2020. The Physiologist completed training and licensing for using Dual Energy X-ray Absorptiometry (DEXA) instrumentation, which will be used to determine effects of the human intervention on body fat and lean tissue composition. The Physiologist also made substantial progress in learning how to use the equipment for measuring resting metabolic rate and physical fitness. Training and standard operating procedures were also developed and refined for use of instrumentation for measuring liver fat (Fibroscan) and blood vessel (arterial) tone (EndoPAT). In support of Objective 1, researchers completed the transfer and implementation of mass spectrometry-based quantitative lipidomic assays and have begun the validation of its use for isolated lipoprotein particle profiling. Methods for the routine in-house kit-based metabolomic analyses, along with data quality assurance/quality control protocols, have also been established and streamlined for use by technical staff. In a subordinate project with the French National Institute for Agricultural Research (INRA) (2032-51530-025-07N) investigating bioactive lipid mediators in plasma lipids as nutrition-sensitive biomarkers of cardio-metabolic health, researchers participated in an international effort with researchers in France, Germany, and Poland to validate plasma esterified bioactive lipids as biomarkers of cardio-metabolic risk. A panel of these lipids was found to have predictive power for the development of cardio-metabolic disease in humans. These results have been presented to the scientific community. Findings suggest that total oxylipin profiling is a valuable tool for cardio-metabolic risk prediction in subjects with preclinical disease and suggests a novel mechanism underlying disease development. Progress on this project supports the parent Sub-objectives 1D and 2C, demonstrating the potential for dietary modulation of esterified bioactive lipids as an important outcome to evaluate the key health-promoting recommendations of the Dietary Guidelines for Americans. In a subordinate project (2032-51530-025-10N) on analytical capabilities, ARS researchers, in collaboration with researchers at the University of California, Davis (UCD) and West Coast Central Comprehensive Metabolomics Resource Core (WC3MRC) have developed novel and efficient methods for the quantitative analysis of various metabolomics components. Methods for the analysis of isoprenylalcohols supporting statin mediated airway inflammation research have been established and used to support research on the UCD campus. A high throughput analysis for the simultaneous determination of approximately 150 lipid mediators, including oxylipins, endocannabinoids, bile acids and steroids, was developed and has been applied locally and nationally in support of cognitive decline and Alzheimer’s disease biomarker discovery. Progress on this project supports the parent Sub-objectives 1D and 2C, while also representing an expansion of the parent project objectives. In a subordinate project with the Pulse Crop Health Initiative (2032-51530-025-49R) on the development of metabolomic biomarkers of pulse intake, ARS researchers, in collaboration with researchers at University of California, Davis, have established routine assays for the quantitative analysis of short-chain fatty acids in human plasma. Progress on this project supports the parent Sub-objectives 1D and 2C, while also representing an expansion of the parent project objectives. In a subordinate project with the National Institute of Food and Agriculture, NIFA, (2032-51530-025-44I) focused on how maternal diet affects the microbiome and susceptibility to metabolic syndrome in offspring, ARS researchers, in collaboration with researchers at University of California, Davis, have designed an experimental protocol and received Institutional Animal Care and Use Committee (IACUC) approval for their studies in mice. Progress on this project supports the parent Sub-objectives 2A and 2B, while also representing an expansion of the parent project objectives. In a subordinate project (2032-51530-025-49R) with the University of Southern California focused on how genetics and diet interact to affect plasma Trimethyl Amine N-oxide production, ARS researchers, in collaboration with researchers at University of California, Davis, have designed an experimental protocol and received Institutional Animal Care and Use Committee (IACUC) approval for their studies in mice. The first cohort of mice (called Diversity Outbred mice) have been purchased and are currently being fed experimental diets. In a subordinate project with the Almond Board of California (2032-51530-025-16T), progress was made by compiling literature on satiety hormones related to energy balance, and a comprehensive review was written. This project expands the research on satiety that supports the parent Sub-objective 1C to determine eating behavior characteristics and satiety response to a meal challenge protocol. In a subordinate project funded by Arla Foods (2032-51530-025-01T), a cohort of 77 participants were selected, and measures related to satiety, food intake, eating behavior, food preferences, and physical characteristics were compiled to create models of satiety for dairy consumers and those who consume very little dairy. This project expands the scope of Sub-objective 1C. Under Objective 3, ARS researchers are collecting human milk and other samples to develop global Reference Values for nutrients in human milk. Investigators in the four country study sites have completed collection of milk, blood, and saliva samples from the majority of the four postpartum visits scheduled for 250 mother-infant dyads during the first eight and one-half months of lactation. COVID cases were relatively few in The Gambia and Denmark, but the sites in Brazil and Bangladesh were profoundly affected. In spite of lock-downs, the field work eventually continued, although at a slower rate of recruitment. In the study, milk volume consumed daily by the infant is measured by the mothers taking a dose of deuterated water, and saliva is collected from mother and infant for 14 days. Deuterium is measured by collaborators at St. John’s Research Institute in Bangalore. In collaboration with researchers at the Children’s Hospital of Zurich, they are measuring iodine in milk, and iodine and thyroid function status in mothers and infants. A majority of the samples from three countries have been received, but additional shipments are pending due to COVID. Overall progress has been delayed due to COVID restrictions, which permit limited access to the laboratory. In spite of these challenges, we plan to finish most nutrient analyses by early 2022. These include newly-developed assays for B vitamins and minerals in milk and plasma, and metabolomics in milk. All data are entered into a database called REDCap at the Medical Research Council site in The Gambia, to which the scientists have access. In 2021 a Data Manager and a statistical consultant were hired to support the project. In 2020, the team submitted a successful new request to the Bill & Melinda Gates Foundation for additional funding to expand analyses, acquire equipment and service contracts, support data analysis and publication meetings, and add a new study on milk composition during the first month postpartum in the same four field sites. The latter study has started in The Gambia, and the remaining three will start recruitment in July, 2021. In a subordinate project (Log# 64716), researchers collaborated with investigators at the University of Colorado in a Gates Foundation-funded micronutrient intervention project in three countries. Supplementation started pre-conception, during pregnancy or during lactation. The ARS role was to analyze B vitamins and choline in breast milk. The sample analyses have been completed, and the main publication is in progress. In a subordinate project with Catholic Relief Services and Harvard University (2032-51530-025-33H), ARS researchers are measuring the differences in micronutrient status in rural Madagascar. The project is examining the effects of different agricultural strategies, including fishing, on micronutrient status of population groups. Lab analyses are complete, and manuscript preparation is in progress. In a subordinate project with the University of Virginia (2032-51530-025-38R), funded by the Gates Foundation, scientists are assessing the effects of niacin supplementation on infant status and development. The niacin analyses have been recently completed after a COVID-related delay.

Accomplishments
1. Increasing dietary fiber in the form of resistant starch wheat may help lower blood glucose. Despite well-documented positive health benefits of consuming dietary fiber, consumption by Americans falls substantially below recommended amounts. Refined wheat is the most common source of grain in our diet, but it is low in dietary fiber. A study by ARS researchers in Davis, California, of healthy adults tested baked products prepared with high resistant starch wheat developed by selective breeding and showed that consuming these baked products for just one-week lowered blood glucose and insulin, increased gut fermentation (breath hydrogen and methane), and altered the fecal microbiome, compared to consuming baked products with conventional refined wheat. Other commercially available forms of resistant starch are used in food products, but the resistant starch wheat is most amenable to baking and will increase the fiber to recommended levels if substituted for regular wheat in baked products. The reduction of glucose and insulin following in response to eating a meal indicates that replacing regular wheat with RS2-enriched wheat may help prevent and potentially manage conditions, such as type 2 diabetes, by controlling rises in glucose and insulin following ingestion of refined carbohydrates.

2. New results in humans provide evidence for a seasonal difference in the relationship between food intake and mental or emotional stress load. An allostatic load is a clinical marker commonly used to assess how the body responds to chronic mental or emotional stress. An increased allostatic load has been linked to chronic disease risk. The factors linking an allostatic load and chronic disease risk are unknown, but possible factors are poor diet or overeating. However, an important question that is still to be sufficiently addressed is whether this relationship between allostatic load and diet varies with the seasons. An observational study by ARS researchers in Davis, California, was conducted to test for seasonal differences in the relationship between allostatic load and daily total consumption of food in 52 women aged 40-60 years. It was found that higher allostatic load is associated with consumption of significantly more calories, carbohydrates, fats, and proteins, but only during the summer and winter seasons, not during fall or spring. These study findings, which were published in the journal, “Stress”, suggest that some women may be more vulnerable to the stress and overeating connection during certain times of the year.

3. Differences in stress system physiology and diet explain variability in stool consistency. Prior studies of adults with constipation or diarrhea suggest that dietary intake, physical activity, and stress may affect stool consistency. However, the influence of these factors is unresolved and has not been investigated in healthy adults. An observational study by ARS researchers in Davis, California, of more than 300 healthy men and women ranging in body weight and age, tested for associations between technician-scored stool consistency and self-reported diet, objectively monitored physical activity, and quantifiable markers of mental and physiological stress load. Hard stool was associated with higher intake of saturated fat and high levels of the stress hormones, cortisol and norepinephrine. However, significantly lower cortisol was associated with softer stool. These findings in healthy adults suggest that managing stress and certain aspects of diet may help prevent the clinical onset of gastrointestinal disturbances.

4. Identifying genetic differences is a key factor when making dietary recommendations for obesity prevention. Obesity results from long-term imbalance between energy intake and expenditure. The mechanisms underlying caloric imbalance are complex and influenced by numerous biological and environmental factors, especially genetics and diet. To determine how consumption of diets with different macronutrient composition alter adiposity and other obesity-related traits in a genetically diverse population, a study was conducted by ARS researchers in Davis, California, to analyze body composition, metabolic rate, clinical blood chemistries, and circulating metabolites. The study was carried out in 22 strains of mice from the Collaborative Cross (CC), a highly diverse recombinant inbred mouse population, before and after eight weeks of feeding either a high protein or high fat high sucrose diet. Findings from this study identified CC strains prone to developing obesity, demonstrate the genotypic and phenotypic diversity of the CC for studying complex traits and highlight the importance of accounting for genetic differences when making dietary recommendations.

5. Weight loss and exercise training affect key lipid mediators of inflammation and energy metabolism in women. Weight loss and fitness influence exercise-associated changes in plasma lipid mediator responses. Endocannabinoids and oxylipins are potent lipid mediators of inflammation and energy metabolism. A study was conducted by ARS researchers in Davis, California, to test the impacts of weight loss and fitness training on the exercise-induced lipid mediator changes in the blood. Acute exercise in sedentary obese women led to a rapid decline in multiple metabolites, with exercise training and weight loss producing more pronounced changes in both endocannabinoid and cytochrome P450 dependent metabolites known to influence vascular health and muscle insulin sensitivity. Therefore, some of the acute and long-term effects of exercise on whole-body physiology may involve local or systemic actions of these classes of regulatory lipids. These findings will be useful for clinicians and the biomedical research community because they help to further clarify the metabolic consequences of weight loss and exercise.

6. Key methodological strategy for improving precision in biochemical analysis of biomedical samples. Epidemiology seeks to link small molecule concentrations to health outcomes in large populations, and modern techniques can measure hundreds to thousands of these compounds simultaneously. How frozen samples are thawed can influence the interpretation of clinically relevant results. A study was conducted by ARS researchers in Davis, California, to investigate the impact of thawing methods on the variability in broad swaths of metabolites present in human serum. It was determined that thawing at room temperature, which results in the fastest thaw, showed the lowest analytical variability in analytes detected. These results are useful for biomedical researchers and provide critical information that will influence the generation of data associated with epidemiological studies attempting to link diet and metabolism to health outcomes.

7. Including sex-specific dietary patterns in health assessments to reduce cardiovascular disease. Among the several factors that influence cardiometabolic disease risk, diet is a modifiable lifestyle parameter associated with a sex/age-specific context. A study was conducted by ARS researchers in Davis, California, to test whether sex differences in dietary patterns could be used alone to identify individuals with or without cardio-metabolic risk factors in men and women. Unique sex/age-specific diet patterns predicted cardio-metabolic risk with high sensitivity and specificity in both women and men. Lower total vegetable intake was associated with the presence of cardio-metabolic risk factors in both sexes. Men with risk factors also had lower intake of greens and beans, while women had a lower intake of fruits, seafood and plant-proteins, fatty acids and saturated fats. Moreover, high dairy intake was associated with the presence of risk factors in women, but not in men. These findings will be invaluable for clinicians and public health policymakers because they help clarify how habitual diet may influence the development of cardiometabolic risk factors in a sex/age-specific manner.

8. New results in mice reveal a key enzyme candidate for linking genetics, diet, and metabolic syndrome. Although mice are an important model in the study of metabolic syndrome, most studies on mice have been conducted with a small number of mouse strains and limited genetic variations. A study by ARS researchers in Davis, California, investigated the diet- or strain-dependence of cardio-metabolic traits in eight Diversity Outbred mice founder strains. The liver transcriptomic analysis of the mouse strains shows that diet and host genetics have profound effects on the liver transcriptome, which may be related to differences in cardo-metabolic traits. Using a network approach, a key enzyme in the production of reactive oxygen species, Nox4, was identified as a candidate affecting plasma Trimethylamine N-oxide (TMAO) and liver triglycerides. These results provide an understanding of the interaction of genetics and diet leading to metabolic syndrome.

9. Defining specific genetic regulation of hepatic gene expression and the influence of diet on gene expression. Genetic approaches in model organisms have consistently demonstrated that molecular traits, such as gene expression, are under genetic regulation, similar to clinical traits. Genetic analysis of two types of gene expression [messenger ribonucleic acid (mRNA) and micro ribonucleic acid (miRNA)] was performed by ARS researchers in Davis, California, in livers from a population of Diversity Outbred mice fed two different diets. The study identified genetic regulation of miRNA and mRNA expression, and key difference in the mode of genetic regulations (cis/trans) were investigated. Results highlight differences in the heritability of mRNA and miRNA and the effects of specific genetic polymorphisms on mRNA and miRNA abundance. The analysis also determined that diet affects the genetic architecture of miRNA and mRNA expression. Overall, these data underscore the complex genetic regulation of two well-characterized ribonucleic acid (RNA) classes (mRNA and miRNA) that have critical roles in the regulation of clinical traits in response to diet.

10. Efficient laboratory methods for the analysis of constituents in human milk. Nutrient concentrations in human milk are recognized to be affected by maternal diet and/or nutritional status, but there are few data on normal values. To provide Reference Values for the usual range of nutrients in milk from well-nourished women, methods for measuring multiple nutrients simultaneously in small volumes of sample were developed and validated by ARS researchers in Davis, California. The methods include near-infrared spectrophotometry, ultra performance liquid chromatography (UPLC)-mass spectrometry, high-pressure liquid chromatography, immunoassays, inductively coupled plasma mass spectrometry, and most recently, targeted metabolomics using commercial kits. These methods are being used to measure milk composition and develop Reference Values in a four-country research project supervised by ARS researchers in Davis, California.

Review Publications
Walker, R.E., Savinova, O.V., Pedersen, T.L., Newman, J.W., Shearer, G.C. 2021. Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low-density lipoproteins in isolated perfused rat livers. Physiological Reports. 9(4). Article e14480. https://doi.org/10.14814/phy2.14480.
Choi, J., Borkowski, K., Newman, J.W., Park, Y. 2021. N-3 PUFA improved post-menopausal depression induced by maternal separation and chronic mild stress through serotonergic pathway in rats – effect associated with lipid mediators. Journal of Nutritional Biochemistry. 91. Article 108599. https://doi.org/10.1016/j.jnutbio.2021.108599.
Dhillon, J., Viscarra, J.A., Newman, J.W., Fiehn, O., Crocker, D.E., Ortiz, R.M. 2021. Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 320(4):R393-R401. https://doi.org/10.1152/ajpregu.00211.2020.
Mainka, M., Dalle, C., Petera, M., Dalloux-Chioccioli, J., Kampschulte, N., Ostermann, A.I., Rothe, M., Bertrand-Michel, J., Newman, J.W., Gladine, C., Schebb, N.H. 2020. Harmonized procedures lead to comparable quantification of total oxylipins across laboratories. Journal of Lipid Research. 61(11):1424-1436. https://doi.org/10.1194/jlr.RA120000991.
Pedersen, T.L., Gray, I.J., Newman, J.W. 2020. Plasma and serum oxylipin, endocannabinoid, bile acid, steroid, fatty acid and nonsteroidal anti-inflammatory drug quantification in a 96-well plate format. Analytica Chimica Acta. 1143:189-200. https://doi.org/10.1016/j.aca.2020.11.019.
Que, E.S., James, K.L., Coffey, A., Smallwood, T.L., Albright, J., Pomp, D., Sethupathy, P., Bennett, B.J. 2020. Genetic architecture modulates diet-induced hepatic mRNA and miRNA expression profiles in Diversity Outbred mice. Genetics. 216(1):241-259. https://doi.org/10.1534/genetics.120.303481.
Yam, P., Albright, J., Verhague, M., Gertz, E.R., Pardo-Manuel De Vill, V., Bennett, B.J. 2021. Genetic background shapes phenotypic response to diet for adiposity in the Collaborative Cross. Frontiers in Genetics. 11. Article 615012. https://doi.org/10.3389/fgene.2020.615012.
Kim, M., Huda, N., O'Connor, A., Albright, J., Durbin-Johnson, B., Bennett, B.J. 2021. Hepatic transcriptional profile reveals the role of diet and genetic backgrounds on metabolic traits in female progenitor strains of the Collaborative Cross. Physiological Genomics. 53(5):173-192. https://doi.org/10.1152/physiolgenomics.00140.2020.
Wegmuller, R., Bentil, H., Wirth, J.P., Petry, N., Tanumihadrjo, S.A., Allen, L.H., Williams, T.N., Selenje, L., Mahama, A., Amaoful, E., Steiner-Asiedu, M., Adu-Afarwuah, S., Rohner, F. 2020. Anemia, micronutrient deficiencies, malaria, hemoglobinopathies and malnutrition in young children and non-pregnant women in Ghana: Findings from a national survey. PLoS ONE. 15(1). Article e0228258. https://doi.org/10.1371/journal.pone.0228258.
Petry, N., Wirth, J.P., Adu-Afarwuah, S., Wegmuller, R., Woodruff, B.A., Tanumihardjo, S.A., Bentil, H., Donkor, W.E., Williams, T.N., Shahab-Ferdows, S., Selenje, L., Mahama, A., Steiner-Asiedu, M., Rohner, F. 2020. Risk factors for anaemia among Ghanaian women and children vary by population group and climate zone. Maternal and Child Nutrition. 17(2). Article e13076. https://doi.org/10.1111/mcn.13076.
Casavale, K.O., Ahuja, J.K., Wu, X., Li, Y., Quam, J., Olson, R., Pehrsson, P.R., Allen, L.H., Balentine, D., Hanspal, M., Hayward, D., Hines, E.P., McClung, J., Perrine, C., Belfort, M.B., Dallas, D., German, D., Kim, J., McGuire, M., McGuire, M. Morrow, A., Nommsen-Rivers, Rasmussen, K.M., Zempleni, J., Lynch, C. 2019. NIH workshop on human milk composition: summary and visions. American Journal of Clinical Nutrition. 110(3):769-779. https://doi.org/10.1093/ajcn/nqz123.
Mazi, T.A., Borkowski, K., Newman, J.W., Fiehn, O., Bowlus, C., Srkar, S., Matsukuma, K., Ali, M.R., Kieffer, D.A., Wan, Y.Y., Stanhope, K.L., Havel, P.J., Medici, V. 2021. Ethnicity-specific alterations of plasma and hepatic lipidomic profiles are related to high NAFLD rate and severity in Hispanic Americans, a pilot study. Free Radical Biology and Medicine. https://doi.org/10.1101/2021.04.08.21254907.
Mercer, K.E., Maurer, A., Pack, L.M., Ono-Moore, K., Spray, B.J., Campbell, C., Chandler, C., Burnett, D., Souza, E., Casazza, G., Keim, N., Newman, J., Hunter, G., Fernadez, J., Garvey, T.W., Harper, M., Hoppel, C., Adams, S.H., Thyfault, J. 2021. Exercise training and diet-induced weight loss increase markers of hepatic bile acid (BA) synthesis and reduce serum total BA concentrations in obese women. American Journal of Physiology - Endocrinology and Metabolism. 320(5):E864-E873. https://doi.org/10.1152/ajpendo.00644.2020.
Hughes, R.L., Horn, W.F., Finnegan, P., Newman, J.W., Marco, M.L., Keim, N.L., Kable, M.E. 2021. Resistant starch type 2 from wheat reduces postprandial glycemic response with concurrent alterations in gut microbiota composition. Nutrients. 13(2):645. https://doi.org/10.3390/nu13020645.
Leslie, E., Lopez, V., Anti, N., Alvarez, R., Kafeero, I., Welsh, D.G., Romero, M., Kaushal, S., Johnson, C.M., Bosviel, R., Blazenovic, I., Song, R., Brito, A., La Frano, M.R., Zhang, L., Newman, J.W., Fiehn, O., Wilson, S. 2021. Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries. American Journal of Physiology - Lung Cellular and Molecular Physiology. 320(5):L770-L784. https://doi.org/10.1152/ajplung.00469.2020.
Grapov, D., Fiehn, O., Campbell, C., Chandler, C.J., Burnett, D.J., Souza, E.C., Casazza, G.A., Keim, N.L., Hunter, G.R., Fernandez, J.R., Garvey, T., Hoppel, C.L., Harper, M., Newman, J.W., Adams, S.H. 2020. Impact of a weight loss and fitness intervention on exercise-associated plasma oxylipin patterns in obese, insulin-resistant, sedentary women. Physiological Reports. 8(17). Article e14547. https://doi.org/10.14814/phy2.14547.
Krishnan, S., Adams, S.H., Allen, L.H., Laugero, K.D., Newman, J.W., Stephensen, C.B., Burnett, D.J., Witbracht, M., Welch, L.C., Que, E.S., Keim, N.L. 2018. A randomized controlled-feeding trial based on the Dietary Guidelines for Americans on cardiometabolic health indexes. American Journal of Clinical Nutrition. 108(2):266-278. https://doi.org/10.1093/ajcn/nqy113.
Kable, M.E., Riazati, N., Kirschke, C.P., Zhao, J., Tepaamorndech, S., Huang, L. 2020. The Znt7-null mutation has sex dependent effects on the gut microbiota and goblet cell population in the mouse colon. PLoS ONE. 15(9). Article e0239681. https://doi.org/10.1371/journal.pone.0239681.
Chin, E.L., Huang, L., Bouzid, Y.Y., Kirschke, C.P., Durbin-Johnson, B., Baldiviez, L.M., Bonnel, E.L., Keim, N.L., Korf, I., Stephensen, C.B., Lemay, D.G. 2019. Association of lactase persistence genotypes (rs4988235) and ethnicity with dairy intake in a healthy U.S. population. Nutrients. 11(8):1860. https://doi.org/10.3390/nu11081860.
Lemay, D.G., Baldiviez, L.M., Chin, E.L., Spearman, S., Cervantes, E., Woodhouse, L.R., Keim, N.L., Stephensen, C.B., Laugero, K.D. 2021. Technician-scored stool consistency spans the full range of the Bristol scale in a healthy US population and differs by diet and chronic stress load. Journal of Nutrition. 151(6):1443-1452. https://doi.org/10.1093/jn/nxab019.
Hampel, D., Shahab-Ferdows, S., Nguyen, N., Gilberto, K., Allen, L.H. 2021. High-throughput analysis of water-soluble forms of choline and related metabolites in human milk by UPLC-MS/MS and its application. Frontiers in Nutrition. 7. Article 604570. https://doi.org/10.3389/fnut.2020.604570.
Anaya-Loyola, M.A., Brito, A., Brown, K.H., Allen, L.H. 2019. Breast milk provides inadequate amounts of vitamin B12 for predominantly breastfed Guatemalan infants. International Journal for Vitamin and Nutrition Research. 90(5-6):395-402. https://doi.org/10.1024/0300-9831/a000583.
Garrod, M.G., Buchholz, B.A., Miller, J.W., Haack, K.W., Green, R., Allen, L.H. 2018. Vitamin B12 added as a fortificant to flour retains high bioavailability when baked in bread. Nuclear Instruments and Methods in Physics Research. 438:136-140. https://doi.org/10.1016/j.nimb.2018.05.042.
Oaks, B.M., Jorgensen, J.M., Baldiviez, L.M., Adu-Afarwuah, S., Maleta, K., Okronipa, H., Sadalaki, J., Lartey, A., Ashorn, P., Ashorn, U., Vosti, S., Allen, L.H., Dewey, K.G. 2019. Prenatal iron deficiency and replete iron status are associated with adverse birth outcomes, but associations differ in Ghana and Malawi. Journal of Nutrition. 149(3):513-521. https://doi.org/10.1093/jn/nxy278.
Haskell, M.J., Young, R., Lartey, A., Eyram Teiko Okronipa, H., Maleta, K., Ashorn, U., Jorgensen, J.M., Yue-Mei, F., Arnold, C., Allen, L.H., Per, A., Dewey, K.G. 2021. Small-quantity lipid-based nutrient supplements do not affect plasma or milk retinol concentrations among Malawian mothers, or plasma retinol concentrations among young Malawian or Ghanaian children in two randomized trials. Journal of Nutrition. 151(4):1029-1037. https://doi.org/10.1093/jn/nxaa439.
Measelle, J.R., Baldwin, D.A., Gallant, J., Chan, K., Green, T.J., Wieringa, F.T., Borath, M., Sophonneary, P., Hampel, D., Shahab-Ferdows, S., Allen, L.H., Kroeun, H., Whitfield, K.C. 2021. Thiamine supplementation holds neurocognitive benefits for breastfed infants during the first year of life. Annals of the New York Academy of Sciences. https://doi.org/10.1111/nyas.14610.
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