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

2023 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. Objective 4: Investigate the health benefits of alternative proteins foods in the context of a healthy diet.

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, continued the human intervention study. Participant recruitment, screening, and enrollment were initiated with 10 participants currently eligible to be enrolled. Four new key personnel were hired for this study. Research staff completed training on devices (EndoPat, Metabolic Carts) that measure vascular health and resting energy expenditure, and on dual x-ray absorptiometry (DEXA) to measure body fat and lean tissue. Substantial protocol modifications were approved by the University of California Davis Institutional Review Board. Diet assessment is being conducted using ASA24. The study database is in REDCap. Planning for collection and processing of specimens was completed. All intervention foods were obtained for menu development. Study test visits were commenced and are ongoing with one participant on the diet intervention. This Objective 1 human intervention study is progressing and is approved to continue in the next project cycle with completion in 2026. In support of Objectives 1 and 2 related to investigation of lipoprotein particle lipidomic profiles, ARS researchers in Davis, California, made critical advances, including: application of quantitative liquid chromatography tandem mass spectrometry lipidomic methods previously transferred from researchers at the Baker Institute of Melbourne, Australia into the Davis ARS laboratory; migration of lipoprotein fractionation and collection techniques onto modern hardware; validation of 96-well plate formats for lipidomic analyses, and measurement of esterified oxylipins in isolated lipoprotein fractions. In a subordinate project (2032-51530-025-65R) funded by the National Institutes of Health characterizing the endogenous function of a recently de-orphaned gene associated with kidney steroid metabolism in humans, ARS researchers in Davis, California, in collaboration with the University of California San Francisco, characterized behavior of the human SLC22A24 and SLC22A10 genes for the ability to transport some 30+ steroids, steroid metabolites, and bile acids. Steroid glucuronides and unconjugated bile acids assays were developed and are being used to analyze plasma and tissues isolated from SLC22A24-transgenic mice. This knowledge will enhance our ability to interpret postprandial changes in lipid and associated metabolism in the parent project dietary interventions under Sub-objective 1B. In a subordinate project (2032-51530-025-076N) investigating metabolomic biomarkers of Alzheimer’s disease risk and progression, ARS researchers in Davis, California, continue to participate in data interpretation and analysis meetings with collaborators at Duke University, the University of California Davis, and the Alzheimer’s Disease Metabolomics Consortium. A manuscript was submitted describing integration of metabolomic markers of metabolism, vascular function and inflammation, and proteomic markers of Alzheimer’s to provide novel insights into the metabolic disruption in this condition. This is an expansion of the parent project Objective 1; Sub-objective 1D. In a subordinate project (0069132) funded by the Foundation for the National Institutes of Health, ARS researchers in Davis, California, in collaboration with researchers at University of California, Davis, are investigating the roles of the soluble epoxide hydrolase and high density lipoprotein-mediated lipid mediator transport in the central nervous system of persons at risk for Alzheimer’s disease. This team demonstrated that soluble epoxide hydrolase inhibitors, in the presence of apolipoprotein E3 suppress formation of lipid autooxidation products in human microglial cells. This project is an expansion of Sub-objective 1D. In a subordinate project (2032-51530-025-044I) funded by National Institute of Food and Agriculture investigating impact of diet and maternal genetics on metabolic syndrome, ARS researchers in Davis, California, in collaboration with the University of California, Davis, generated bodyweight and phenotypic data in a cohort of genetically diverse mice. Initial data suggests a significant effect of maternal genotype on metabolic syndrome risk. This project expands parent project Sub-objective 2A. In a subordinate project (2032-51530-025-049R), ARS researchers in Davis, California, in collaboration with researchers at University of California, Davis, performed a meta-analysis from five different studies of the genetic regulation of trimethylamine N-oxide (TMAO) in 1,482 female and male Diversity Outbred mice aged 6 to 44 weeks. Data analysis identified a region of Chromosome 12 (Chr 12) associated with fasting plasma TMAO. Further analysis suggested alleles inherited from the Cast/EiJ (CAST) and PWK/PhJ (PWK) mouse strains within the Chr 12 quantitative trait loci (QTL) reduced TMAO concentrations. Genes within the Chr 12 QTL have synteny with humans and may translate to the genetic regulation of human plasma TMAO concentrations and atherosclerosis. Gene by sex and gene by diet interactions regulating plasma TMAO have important ramifications for genome-wide association studies (GWAS) assessing complex traits in humans. In support of Objective 3, to establish Reference Values (RVs) for vitamins and minerals in human milk, ARS scientists in Davis, California, continued with funding support for the Mothers, Infants and Lactation Quality (MILQ) study from the Bill & Melinda Gates Foundation (2032-51530-025-077H). In fiscal year (FY) 2023, methods for analysis of 13 macro- and trace elements in milk were developed and applied using an Inductively Coupled Plasma-Mass Spectrometer. Of the 2,574 milk samples collected in four country sites through FY 2022, analyses are 100 percent (%) complete for B vitamins, macronutrients, metabolomics, and minerals. In FY 2023 significant progress was also made in data management and graphical expression of pooled milk nutrient data from the four research sites. Final curves of nutrient concentrations across the first 8.5 months of lactation generated median and key percentiles, using penalized B-spline curves with GAMLSS (Generalized Additive Models for Location, Scale and Shape) in R, to obtain graphs that can be uniformly used across nutrients. Preliminary results were shared at two in-person meetings with co-Investigators in FY 2023. In support of Sub-objective 3B, a follow-on study (2032-51530-025-039T) during the first month of lactation, ARS researchers in Davis, California, have collected additional milk and plasma from 65 maternal-infant dyads in each of the same four MILQ sites. Analyses will start late 2023. In a subordinate study (2032-51530-025-085H), ARS researchers in Davis, California, analyzed effects on milk of micronutrient (MN) supplements given by collaborators at Johns Hopkins University to Bangladeshi women during pregnancy and three months of lactation. Supplementation with 15 nutrients increased riboflavin, niacin and vitamin B6 in milk but not thiamin, and showed supplements have to be continued during lactation to improve milk MN. A subordinate study (2032-51530-025-61T) based at Kings College London/Medical Research Council Gambia, is providing MN supplements to pregnant and/or lactating mothers in The Gambia to determine timing that best improves infant MN status and development. MN will be analyzed by ARS scientists in Davis, California, and compared to our new RVs. A subordinate study (2032-51530-025-090H) by Harvard University compared regular vs high dose (three times recommendations) supplementation with multiple MN in pregnancy and/or lactation on maternal and infant B vitamin status in Tanzania. The milk is measured by ARS scientists in Davis, California. The first article reports a high prevalence of low milk B12, improved by maternal B12 supplementation in either pregnancy or lactation. Response will be compared to our new RVs. In a subordinate study (2032-51530-025-077H), ARS scientists in Davis, California, are collaborating with the International Milk Composition Consortium (IMiC) to analyze MN in human milk collected from nutritional supplement interventions in 4 countries. Analyses are nearly complete and results were shared with IMiC in Gent, Belgium, June 2023. Results will be compared to our new RVs.

Accomplishments
1. Stress may accentuate age-related deregulation of immune system over-activity. Frequencies and functional capacities of immune cells typically decrease with aging, a process referred to as immunosenescence. A prolonged or enhanced physiological response to psychological stressors may accelerate this age-associated decline in the immune system. A study by ARS researchers in Davis, California, was conducted to delineate the contribution of cumulative physiological stress load on immunosenescence in a cohort of healthy volunteers ranging in age from 18-66 years. Findings from this study suggest that, if unchecked or prolonged, physiological adjustments in response to psychological stressors may accentuate age-related reduction of Treg frequencies in younger people, possibly increasing vulnerability to immune system over-activity and related autoimmune disease. This work adds new information to a body of work that supports chronic stress as a risk factor for conditions (e.g., autoimmune disease) linked to immune system over-activity.

2. A sugar-rich diet associated with lower decision-making performance and higher chronic stress. The executive brain mediates and facilitates a set of cognitive functions, such as decision-making, planning, self- and emotional-regulation, and attention. The executive brain is particularly vulnerable to effects of psychological stress, and chronic stress, executive brain dysfunction, and related age-associated diseases such as Alzheimer’s disease are a rising public health concern. A study by ARS researchers in Davis, California, compared the influence of different diet patterns on executive brain function by using a cognitive test that specifically probes a person’s ability to effectively weigh short-term reward with long-term consequences. A diet pattern characterized by elevated sugar-sweetened beverage and added sugar consumption was associated with the lowest decision-making performance, higher self-reported psychological stress exposure, and alterations in the autonomic nervous system activity. Diet patterns defined by more fruits and vegetables or higher omega-3 fatty acids and seafood associated with lower chronic stress exposure. Results from this study provide new information that further supports the potential importance of whole diet patterns on cognitive disease prevention.

3. Trimethoprim impacts tissue thiamine status by inhibition of liver and kidney cation transporters. Trimethoprim, an antibiotic used to treat urinary tract infections, is predicted to inhibit several thiamine transporters and may affect concentrations of this vitamin critical for energy metabolism in a tissue-specific manner. A study by ARS researchers in Davis, California, and Boston, Massachusetts, in collaboration with colleagues at the University of California campuses in San Francisco and Davis, California, studied the impact of trimethoprim on thiamine absorption in cells in humans and mice. Despite trimethoprim’s ability to inhibit the transporter primarily responsible for thiamine absorption in the gut, this drug increased blood concentrations of thiamine. Further investigations in mice and humans suggest that trimethoprim inhibits thiamine absorption in the liver resulting in elevations in triglycerides, low density lipoprotein cholesterol and total cholesterol in the blood. These findings highlight the potential for complex drug-nutrient interactions that involve transporters as previously demonstrated for drug-drug interactions.

4. An obesity assessment tool for low-income, Spanish-speaking clients will aid in identifying families at risk. The prevalence of obesity and morbidities in Latino families poses health risks to this growing ethnic group. In collaboration with colleagues at the University of California and California State University Sacramento, ARS researchers in Davis, California, established that a unique pictorial tool was valid and reliable for reporting nutrition, physical activity, screen time and sleep behaviors related to obesity risk. Cooperative extension specialists are using this for research purposes now, but it will be used in future studies to assess obesity risk.

5. Systems genetic approach identifies novel genes and pathways associated with cardiovascular disease. Atherogenesis is the formation of lesions in arteries leading to many of the serious consequences of cardiovascular diseases (CVD). In collaboration with colleagues at the University of California and The University of North Carolina, Chapel Hill, ARS researchers in Davis, California, identified novel loci associated with atherosclerosis using a genetically diverse genetic panel of atherosclerosis susceptible mice. All mice had two human genes: encoding apolipoprotein E3-Leiden and cholesterol ester transfer protein to induce atherosclerosis susceptibility. The expression of genes was assessed by ribonucleic acid (RNA)-sequencing, and several genes were highly correlated with the atherogenic traits. Integrative analysis identified Ptprk and Cyp2c67 as major candidate genes affecting the size of atherosclerotic lesions. Finally, through additional analyses of RNA-sequencing data, researchers identified genetic regulation of a hepatic transcription factor, Nr1h3, that contributes to atherogenesis. Thus, an integrative approach using DO-F1 mice effectively validates the influence of genetic factors on atherosclerosis in DO mice and suggests an opportunity to discover therapeutics in the setting of elevated blood lipids.

6. Trimethylamine N-Oxide response to a mixed macronutrient tolerance test varies in a cohort of healthy U.S. adults. Animal foods like red meat, eggs, fish and dairy contain compounds that when eaten as part of the diet leads to increases in trimethylamine n-oxide (TMAO) in the blood, but it is unknown whether TMAO amounts change following a mixed macronutrient tolerance test (MMTT). A study by ARS researchers in Davis, California, provided healthy female and male adults a MMTT (60 percent (%) fat, 25% sucrose; 42% of a standard 2000 kilocalorie diet) and recorded their metabolic response at fasting and at 30 minutes, three hours, and six hours after a meal. Total exposure to TMAO in the circulation over six hours was determined and individuals classified by the blood draw at which they experienced their maximal TMAO concentration (TMAO-response groups). The researchers observed an important relationship between six-hour exposure to TMAO and an inflammatory marker, TNF-a, that depended on TMAO-response group. These findings promote precision nutrition and have important ramifications for the eating behavior of adults who could benefit from reducing TMAO exposure, and for understanding factors that generate plasma TMAO and inflammation following meals.

7. The health effect of diet varies by genetics and microbiota within inbred mice. Metabolic diseases are major public health issues worldwide and are responsible for disproportionately higher healthcare costs. A study by ARS researchers in Davis, California, in collaboration with colleagues at Texas A+M modeled the complex relationship between host genetics, gut microbiota, and dietary patterns using inbred mice. They treated four widely used metabolically diverse inbred mouse strains with four human-relevant diets and a control mouse chow from 6 weeks to 30 weeks of age. They identified diet-induced alterations of gut microbiota (a-diversity, ß-diversity, and abundance of several bacteria including Bifidobacterium, Ruminococcus, Turicibacter, Faecalibaculum, and Akkermansia) is significantly modified by host genetics. In addition, depending on the gut microbiota, the same diet could have different metabolic health effects. These data demonstrate the complex interactions between host genetics, gut microbiota, and diet on metabolic health, and provide new information supporting the need to consider both host genetics and the gut microbiota in the development of new and more effective precision nutrition strategies to improve metabolic health.

8. Genetics alters the response to dietary macronutrient composition through a complex hepatic transcriptional network. Obesity is a serious disease with a complex etiology characterized by over-accumulation of body fat resulting in detrimental health outcomes. In collaboration with colleagues at the University of California and The University of North Carolina, Chapel Hill, ARS researchers in Davis, California, identified over 1000 genes differentially expressed by perturbed dietary macronutrient composition. These data utilized mice from 22 strains of the genetically diverse recombinant inbred Collaborative Cross (CC) mouse panel to determine how genetics and diet impact obesity development. Whole genome expression data was subjected to network analysis which identified multiple gene clusters (modules) associated with body fat percentage. Changes in macronutrient composition altered gene expression related to metabolic processes, while genetic background heavily influenced a broad range of cellular functions and processes irrespective of body fat content. These new dietary findings clarify the individual role of macronutrient composition, genetics, and their interaction, which is critical to developing therapeutic strategies and policy recommendations for precision nutrition.

9. Developed methods for simultaneous analysis of macro-minerals and trace-elements in low volumes of human milk. Adequate concentrations of human milk macro- and trace-elements are crucial for breastfeeding infant’s healthy growth and development. ARS investigators in Davis, California, developed a method for simultaneously analyzing selective macro- and trace-elements in sub-milliliter amounts of human milk by inductively-coupled plasma-mass spectrometry (ICP-MS), covering a range from 0.1 parts per billion to 30 parts per million. After modifications to reduce interference from the milk matrix and various ions, all elements can be measured precisely except for those present in minute amounts (chromium, molybdenum, manganese). Analysis of approximately 1000 milk samples from well-nourished mothers in four countries has been completed and these new data can be used to improve estimated mineral requirements of breastfeeding infants and their mothers.

10. Evaluation of criteria, including breast milk iodine concentration, used to assess iodine status in lactating women and infants. In collaboration with experts in global assessment and measurement of iodine status at University Children’s Hospital in Zurich, Switzerland, ARS scientists in Davis, California, used milk, plasma and urine from 1000 women and their infants in four countries as part of the Maternal, Infant and Lactation Quality study. The goal was to establish thresholds for breast milk and urinary iodine concentration during lactation since no World Health Organization-accepted values exist. All countries had mandatory Universal Salt Iodization but at different levels. Thyroglobulin levels were increased in two countries indicating mild iodine deficiency but thyroid stimulating hormone and thyroxine were normal in all sites. Investigators concluded that breast milk iodine concentration is a good reflection of recent iodine intake, is an accurate biomarker for population iodine status, and should be measured rather than urinary iodine concentration in lactation.

11. Maternal inflammation, body mass index and metabolic indicators in pregnancy predict birthweight, and cytokines and leptin in milk. In collaboration with scientists at the University of Copenhagen, Denmark, human milk and maternal plasma samples from the Mothers, Infants and Lactation Quality study were analyzed by ARS scientists in Davis, California, for indicators of maternal inflammation including multiple cytokines and biomarkers of metabolic dysfunction. Maternal high density lipoproteins at 28 weeks of pregnancy were negatively correlated with gestational age and infant birthweight but triglycerides and glucose were positively associated with birthweight. Higher maternal body mass index predicted higher concentrations of inflammatory cytokines in milk samples during lactation, and maternal plasma leptin in pregnancy was associated with milk leptin. The data suggest important effects of maternal pregnancy metabolism and inflammation that continue to affect milk composition postpartum.

Review Publications
Rybak, I., Haas, K., Dhaliwal, S., Burney, W., Pourang, A., Sandhu, S.S., Maloh, J., Newman, J.W., Crawford, R., Sivamani, R.K. 2023. Prospective placebo-controlled assessment of spore-based probiotic supplementation on sebum production, skin barrier function, and acne. Journal of Clinical Medicine. 12(3). Article 895. https://doi.org/10.3390/jcm12030895.
Bellomo, T.R., Tsao, N.L., Johnston-Cox, H., Borkowski, K., Shakt, G., Judy, R., Moore, J., Ratcliffe, S., Fiehn, O., Floyd, T.F., Wehrli, F.W., Mohler, E., Newman, J.W., Damrauer, S.M. 2022. Metabolite patterns associated with individual response to supervised exercise therapy in patients with intermittent claudication. Journal of Vascular Science. 3:379-388. https://doi.org/10.1016/j.jvssci.2022.10.002.
Dalle, C., Tournayre, J., Mainka, M., Basiak-Rasala, A., Pétéra, M., Lefèvre-Arbogast, S., Dalloux-Chioccioli, J., Deschasaux-Tanguy, M., Lecuyer, L., Kesse-Guyot, E., Fezeu, L., Hercberg, S., Galan, P., Samieri, C., Zatonska, K., Calder, P.C., Hjorth, M., Astrup, A., Mazur, A., Bertand-Michel, J., Schebb, N.H., Szuba, A., Touvier, M., Newman, J.W., Gladine, C. 2022. The plasma oxylipin signature provides a deep phenotyping of metabolic syndrome complementary to the clinical criteria. International Journal of Molecular Sciences. 23(19). Article 11688. https://doi.org/10.3390/ijms231911688.
Ahmadi, A., Huda, M., Bennett, B.J., Gamboa, J., Zelnick, L., Smith, L.R., Chondronikola, M., Raftery, D., de Boer, I.H., Roshanrvan, B. 2022. Chronic kidney disease is associated with attenuated plasma metabolome response to oral glucose tolerance testing. Journal of Renal Nutrition. 33(2):316-325. https://doi.org/10.1053/j.jrn.2022.09.013.
Bragg, M., Prado, E., Caswell, B.L., Arnold, C., George, M., Oakes, L., Beckner, A., DeBolt, M., Bennett, B.J., Maleta, K., Stewart, C. 2022. The association between plasma choline, growth and neurodevelopment among Malawian children aged 6-15 months enrolled in an egg intervention trial. Maternal and Child Nutrition. 19(2). Article e13471. https://doi.org/10.1111/mcn.13471.
Perrin, M.T., Mansen, K., Israel-Ballard, K., Richter, S., Bode, L., Hampel, D., Shahab-Ferdows, S., Allen, L.H., Cofre Maggio, F., Njuguna, E., Tran, H., Wesolowska, A. 2023. Investigating donor human milk composition globally to develop effective strategies for the nutritional care of preterm infants: Study protocol. PLOS ONE. 18(4). Article e0283846. https://doi.org/10.1371/journal.pone.0283846.
Christensen, S.H., Lewis, J.I., Larnkjær, A., Frøkiær, H., Allen, L.H., Mølgaard, C., Michaelsen, K.F. 2022. Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes. Frontiers in Nutrition. 9. Article 1025439. https://doi.org/10.3389/fnut.2022.1025439.
James, K.L., Gertz, E.R., Kirschke-Schneide, C.P., Allayee, H., Huang, L., Kable, M.E., Newman, J.W., Stephensen, C.B., Bennett, B.J. 2023. Trimethylamine N-Oxide response to a mixed macronutrient tolerance test in a cohort of United States adults. International Journal of Molecular Sciences. 24(3). Article 2074. https://doi.org/10.3390/ijms24032074.
Lee, J., Purello, C., Booth, S.L., Bennett, B.J., Wiley, C., Korstanje, R. 2023. Chow diet in mouse aging studies: Nothing regular about it. GeroScience. 45:2079-2084. https://doi.org/10.1007/s11357-023-00775-9.
Johnson, C.N., Arsenault, R.J., Piva, A., Grilli, E., Swaggerty, C.L. 2023. A microencapsulated feed additive containing organic acids and botanicals has a distinct effect on proliferative and metabolic related signaling in the jejunum and ileum of broiler chickens. Frontiers in Physiology. 14. Article 1147483. https://doi.org/10.3389/fphys.2023.1147483.
Yam, P., VerHague, M., Albright, J., Gertz, E.R., Manuel-de-Villena, F., Bennett, B.J. 2022. Altered macronutrient composition and genetics influence the complex transcriptional network associated with adiposity in the Collaborative Cross. Genes and Nutrition. 17. Article 13. https://doi.org/10.1186/s12263-022-00714-x.
Huda, M.N., Salvador, A.C., Barrington, W.T., Gacasan, C.A., D'Souza, E.M., Deus Ramirez, L., Threadgill, D.W., Bennett, B.J. 2022. Gut microbiota and host genetics modulate the effect of diverse diet patterns on metabolic health. Frontiers in Nutrition. 9. Article 896348. https://doi.org/10.3389/fnut.2022.896348.
Kim, M., Huda, N., Evans, L.W., Que, E., Gertz, E.R., Maeda-Smithies, N., Bennett, B.J. 2023. Integrative analysis of hepatic transcriptional profiles reveals genetic regulation of atherosclerosis in hyperlipidemic Diversity Outbred-F1 mice. Scientific Reports. 13. Article 9475. https://doi.org/10.1038/s41598-023-35917-8.
Wang, Y.E., Kirschke-Schneide, C.P., Woodhouse, L.R., Bonnel, E.L., Stephensen, C.B., Bennett, B.J., Newman, J.W., Keim, N.L., Huang, L. 2022. SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults. Biomed Central (BMC) Nutrition. 8. Article 95. https://doi.org/10.1186/s40795-022-00592-x.
Henjum, S., Groufh-Jacobsen, S., Allen, L.H., Raael, E., Israelsson, A., Shahab-Ferdows, S., Hampel, D. 2022. Adequate vitamin B12 and folate status of Norwegian vegans and vegetarians. British Journal of Nutrition. 129(12):2076-2083. https://doi.org/10.1017/S0007114522002987.
Diana, A., Rahmannia, S., Suhadi, Y.Z., Luftimas, D.E., Rizqi, H., Purnamasari, A.D., Jihadillah, A., Ansari, M.B., Haq, D.A., Pratiwi, A.N., Scott, S., Hampel, D., Allen, L.H., Haszard, J.J., Houghton, L.A., Gibson, R.S., Fahmida, U. 2022. Chicken liver and eggshell crackers as a safe and affordable animal source food for overcoming micronutrient deficits during pregnancy and lactation in Indonesia: A double-blind, randomised placebo-controlled trial (SISTIK growth study). Wellcome Open Research. 7. Article 167. https://doi.org/10.12688/wellcomeopenres.17879.1.
Batalha, M.A., dos Reis Costa, P.N., Ferreira, A.L., Freitas-Costa, N.C., Figueiredo, A.C., Shahab-Ferdows, S., Hampel, D., Allen, L.H., Perez-Escamilla, R., Kac, G. 2022. Maternal mental health in late pregnancy and longitudinal changes in postpartum serum vitamin B-12, homocysteine, and milk B-12 concentration among Brazilian women. Frontiers in Nutrition. 9. Article 923569. https://doi.org/10.3389/fnut.2022.923569.
Watkins, B., Newman, J.W., Kuchel, G.A., Fiehn, O., Kim, J. 2023. Dietary docosahexaenoic acid and glucose systemic metabolic changes in the mouse. Nutrients. 15(12). Article 2679. https://doi.org/10.3390/nu15122679.
Vora, B., Wen, A., Yee, S., Trinh, K., Azimi, M., Green, E.A., Sirota, M., Greenberg, A.S., Newman, J.W., Giacomini, K.M. 2023. The effect of trimethoprim on thiamine absorption: A transporter-mediated drug-nutrient interaction. Clinical Pharmacology and Therapeutics. 114(2):381-392. https://doi.org/10.1002/cpt.2932.
Snoke, D., Angelotti, A., Borkowski, K., Cole, R., Newman, J.W., Belury, M.A. 2022. Linoleate-rich safflower oil diet increases linoleate-derived bioactive lipid mediators in plasma, and brown and white adipose depots of healthy mice. Metabolites. 12(8). Article 743. https://doi.org/10.3390/metabo12080743.
Angelotti, A., Snoke, D., Ormiston, K., Cole, R., Borkowski, K., Newman, J.W., Orchard, T., Belury, M.A. 2022. Potential cardioprotective effects and lipid mediator differences in long-chain omega-3 polyunsaturated fatty acid supplemented mice given chemotherapy. Metabolites. 12(9). Article 782. https://doi.org/10.3390/metabo12090782.
Johnson, C.M., Rosario, R., Brito, A., Agrawal, K., Fanter, R., Lietz, G., Haskell, M., Engle-Stone, R., Newman, J.W., La Frano, M.R. 2022. Multiassay nutritional metabolomics profiling of low vitamin A status versus adequacy is characterized by reduced plasma lipid mediators among lactating women in the Philippines: A pilot study. Nutrition Research. 104:118-127. https://doi.org/10.1016/j.nutres.2022.05.007.
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