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

2022 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, tested usability of continuous glucose and physical activity monitors, which will inform the best use of these methods in the Objective 1 human intervention study. A test of Objective 1 experimental protocols and staff training was also completed. That protocol development and training clarified and improved standard operating procedures and testing logistics for evaluating body height and weight, heart rate, blood pressure, body composition, meal-induced metabolic response, metabolic rate, appetite, vascular function, liver health, body strength, physical fitness, and mental stress responsiveness. The Clinical Research Oversight Committee approved the analysis of screening blood tests at the University of California Davis Health Pathology Lab in Sacramento, California. Study personnel also decided on a method for prescribing the caloric content of each participants’ intervention diets in the Objective 1 study. The developmental study established test visit timing parameters, equipment calibration, and acquainted research staff with new equipment for the Objective 1 human study. A procedure was created for handling deviations from weight stability in participants assigned to the weight stable Dietary Guidelines for Americans diet intervention under Objective 1. Progress was also made in establishing the database for storing study data collected in the Objective 1 intervention study. In a subordinate project (2032-51530-025-35R) investigating therapeutic interference with thiamine uptake and metabolism in humans, ARS researchers in Davis and Boston (Tufts University), in collaboration with researchers at University of California, Davis, and the University of California, San Francisco, evaluated the impact of metformin and trimethoprim on thiamine uptake kinetics, and metabolomics responses in humans. ARS researchers in Davis analyzed trimethoprim, metformin and thiamine vitamers and metabolomic profiles in human and mouse samples. ARS researchers in Davis determined thiamine transporter 2 is important for maintaining thiamine levels in the brain. A study was performed in mice to evaluate the metabolome-wide impact of thiamine deficiency. Progress on this project represents an expansion of the parent project objectives under Objective 1 relating to variability in response to dietary intake. In a subordinate project with the Pulse Crop Health Initiative (2032-51530-025-49R) on the development of metabolomics biomarkers of pulse intake, ARS researchers, in collaboration with researchers at University of California, Davis, developed and tested research diets, submitted and received study approval for the Institutional Review Board (IRB), and begun participant recruitment. Progress on this project supports the parent Sub-objectives 1D and 2C, and represents an expansion of the parent project objectives. In a subordinate project (2032-51530-025-65R) characterizing the endogenous function of a gene associated with human kidney steroid metabolism, ARS researchers in Davis, in collaboration with researchers at University of California, San Francisco, characterized the human SLC22A24, a transporter gene, for the ability to transport 30+ steroids, steroid metabolites, and bile acids. Steroid glucuronides and unconjugated bile acids appear to be preferred substrates. This knowledge will enhance our ability to interpret postprandial changes in lipid and lipid associated metabolism in subjects enrolled in the parent project under Objective 1, 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 participated in data interpretation and analysis meetings with collaborators at Duke University, the University of California, Davis, and other members of the Alzheimer’s Disease Metabolomics Consortium. Metabolomics markers of metabolism, vascular function and inflammation were integrated with proteomic markers of Alzheimer’s disease, which provided novel insights into the metabolic consequences of the disease. Results were presented to the research community. This project enables exploration of the metabolic perturbation of key regulatory components of cardiometabolic health. Project progress represents an expansion of the parent project Sub-objective 1D. In a subordinate project (000006752) evaluating the influence of lipoprotein-mediated transport of bioactive lipids in Alzheimer's disease, ARS researchers in Davis provided input to researchers at University of California regarding experimental designs and data interpretation. This team identified unexpected links between inhibitors of soluble epoxide hydrolase metabolism, the action of lipoxygenase metabolism, and the production of inflammatory cytokines in human microglial cell cultures. Progress on this project represents an expansion of Sub-objective 1D. In a subordinate project with the Almond Board of California (2032-51530-025-16T), a comprehensive review of peripheral satiety hormones was published, and information will be used to construct satiety models potentially unique to high-protein, high-fiber snacks. 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. Under Objective 3, ARS researchers are collecting human milk and other samples to develop global reference values for human milk nutrients. Investigators in 4 study sites (Denmark, Brazil, Bangladesh, and The Gambia) completed collection of milk, blood, and saliva samples from the 4 postpartum visits scheduled for 250 mother-infant dyads during the first 8.5 months of lactation. A unique aspect of the study is milk volume consumed daily by infants is measured by giving deuterated water to the mothers. Deuterium is measured at St. John’s Research Institute in Bangalore, Bangladesh. Analysis for the Brazil samples is complete. In collaboration with Children’s Hospital of Zurich, we are measuring iodine in milk, and iodine and thyroid function status in mothers and infants. Analyses are complete for Denmark and Brazil. This sub-study will determine relationships between maternal iodine status, milk iodine and infant status and may change international recommendations for iodine status biomarkers. All except one batch of samples from Bangladesh were received by the ARS research team. The total number of analyses of milk completed in FY22 was 1734 vitamin B12, thiamin, other B vitamins and macronutrients; 310 plasma B12, vitamin D and folate; and 1700 for markers of inflammation. Most nutrient analyses will be completed by early 2023 after which the Reference Values will be published. With funds from the Bill & Melinda Gates Foundation an ICP-MS (inductively coupled plasma mass spectrometry) and microwave digestor were purchased for the analysis of minerals in milk and plasma. All data are entered into a REDCap database at the Medical Research Council site in The Gambia. A Data Manager and a statistical consultant were hired in Davis, California, to support the project. The Data Manager checked consistency of variable names across sites and worked with sites on initial analysis of anthropometry, anemia, and infant development data. There are 94 “priority” and 3174 total variables for data collected at field sites plus biomarker data produced by the Davis ARS research team. A “Data Cleaning Principles” document was created and a data analysis meeting will be held in Cambridge, UK, September 2022. In 2020, the team received additional funding for a new study on milk composition during the first month postpartum in the same four field sites. The study was completed in 3 sites and will be finished within 3 months in the fourth site. Analysis of these samples will start in 2023. An agreement was established with the University of California, Davis, to analyze human milk oligosaccharides and bioactive proteins. A separate agreement was established with researchers in Cambridge, UK, to analyze vitamin D in milk. A “Dietary Analysis” team was instituted by the ARS researchers and representatives from the four study sites. DNA was extracted from infant feces and RNA is being extracted from milk for genotyping. An additional sub-study in Denmark measured satiety hormones and cytokines to test their associations with infant milk intake, infant growth and body composition, as well as maternal determinants. Similar analyses will be made on samples from the other 3 sites if funding permits. In a subordinate project with the University of Virginia (2032-51530-025-38R), funded by the Bill & Melinda Gates Foundation, scientists are assessing the effects of niacin supplementation on infant status and development in Tanzania. The niacin analyses were completed by ARS investigators in Davis, California, and manuscript preparation is in progress. In a subordinate project with John Hopkins University (2032-51530-025-085H) funded by the Bill & Melinda Gates Foundation, ARS researchers in Davis, California, are analyzing B vitamins in milk collected from a trial in Bangladesh. In 752 human milk samples collected at 3 months postpartum, we are analyzing the effects on milk micronutrients of providing multiple micronutrient supplements vs iron and folic acid from pre-conception through 3 months of lactation.

Accomplishments
1. The stress hormone cortisol may limit cholesterol lowering effects of consuming a healthy diet. Cortisol concentrations in the body fluctuate throughout the day, and this steroid hormone has important effects on behavior and body metabolism. However, person-to-person differences in cortisol levels during certain times of the day may help to explain why some people respond or do not respond to nutrition interventions aimed at improving metabolic health. A study by ARS researchers in Davis, California, was conducted to test whether the magnitude of cortisol concentrations during certain times of the day modified effects of a healthy diet on clinical markers of metabolic health. Results from this study showed that compared to a more typical American high fat and sugar diet, a Dietary Guidelines for Americans (DGA)-based diet reduced total and low-density lipoprotein (LDL) cholesterol, but this potentially beneficial effect of the DGA was inhibited in participants who also had high morning concentrations of circulating cortisol. These findings suggest that the cholesterol-lowering effect of a DGA diet is sensitive to variations in morning cortisol status and imply that stress or other factors that significantly elevate morning cortisol may limit some effects of whole food diets to reduce cardiovascular disease risk.

2. A healthy diet pattern changes protein function. Metabolomics is the study of small molecules, including proteins, and is an important aspect of understanding the impact of diet on health. Proteins can be modified many ways within the cell, and modifications can change their functions, but nothing is known about how a complete, high-quality diet based on the Dietary Guidelines for Americans (DGA) might affect protein modification. To evaluate the effect of the DGA diet, ARS researchers in Davis, California, collaborated with researchers at the University of California, Davis, to measure specific glycoproteins that have previously been associated with cardiometabolic risk. The results indicate that DGA was associated with a higher sialic acid (a sugar added by glycosylation) content of proteins compared to the low-quality diet. This is the first report of diet quality impacting glycosylation in humans. Since a higher sialic acid content of proteins is known to sustain and support its function and influence the rate at which proteins are cleared from the body, this new evidence establishes that a high quality diet affects glycosylation and provides key information that advances the relatively new line of health research linking diet, glycosylation, and health.

3. Response to consuming long-chain omega-3 fatty acids is influenced by adiposity in overweight to obese women. The Dietary Guidelines for Americans (DGA) recommends consuming approximately 225 grams per week of a variety of seafood, which provides more than 1.75 grams per week of long-chain omega-3 fatty acids (OM3) to reduce cardiovascular disease risk. However, individual responses to omega-3 fatty acid treatments can vary for reasons not well understood. ARS researchers in Davis, California, conducted an eight week feeding study in overweight to obese women to: 1) determine if a DGA-conforming diet (DGAD), in comparison to a typical American diet (TAD), can improve omega-3 status; 2) to identify factors explaining variability in the OM3 response to diet; and 3) to identify factors associated with the baseline OM3 status. Study results show that consuming three meals per week containing fatty cold-water fish for eight weeks improved the OM3 status, but response magnitude was variable. Generally, women starting the study with a lower OM3 status improved more over the study, with a lower initial status being associated with a lower reported habitual intake of OM3 fatty acids as a proportion of total dietary fat consumed, and higher levels of fat around the body trunk, chest and upper arms referred to as central fat. These findings support food recommendations in the DGA designed to increase an individual’s omega-3 fatty acid status to reduce cardiovascular risk and indicate that increased OM3 consumption may be more effective in individuals with a predominance of central fat, which is a cardiovascular disease risk factor.

4. Plasma trimethylamine N-oxide (TMAO) associated with markers of inflammation in metabolically healthy Americans. Trimethylamine N-oxide (TMAO), a metabolite of dietary choline generated by the gut microbiota, has been associated with cardiovascular disease (CVD). A study by ARS researchers in Davis, California, was conducted to assess drivers of TMAO variation by studying diet, the fecal microbiome, and cardiometabolic markers, which are known cornerstones of the TMAO pathway, in a generally healthy cohort of adults. TMAO concentrations were generally not associated with intake of specific foods but were related to the fecal microbiome, specifically the abundance of the genera Butyrivibrio, Roseburia, Coprobaciullus, and Catenibacterium. Unexpectedly, in this generally healthy cohort, TMAO was not associated with classic cardiovascular risk factors such as plasma lipids or measures of endothelial function. Tumor necrosis factor a (TNFa) was significantly associated with plasma TMAO in individuals in the lowest versus the highest TMAO tertile, suggesting that subjects with higher TMAO have increased systemic inflammation.

5. High-fat diets can negatively alter certain gastrointestinal cells, leading to enhanced production of TMAO. A collaborative study that included ARS researchers in Davis, California, was conducted to test if chronic exposure to a high-fat diet affects trimethylamine N-oxide (TMAO) generation through specific microorganisms (microbiota), such as the bacteria Escherichia coli (E. coli), which inhabit the gastrointestinal tract. A series of experiments in mice demonstrated that a high fat diet increased E. coli-derived choline metabolism in the gastrointestinal tract. This altered metabolism in E. coli increased circulating levels of the potentially harmful metabolite, TMAO, in the body. These data suggest that synergistic metabolism by both the gastrointestinal microbiota and intestinal cells in response to a high fat diet can affect plasma TMAO levels.

6. Lower meat intake reduces trimethylamine N-oxide levels in adults consuming a Mediterranean diet. A Mediterranean-style eating pattern (MED-EP) may include moderate red meat intake. However, it is unknown if the pro-atherogenic metabolite trimethylamine N-oxide (TMAO) is affected by the amount of red meat consumed with a MED-EP. In an investigator-blinded, randomized, crossover, controlled feeding trial, ARS scientists in Davis, California, showed that lower intake of lean red meat in the context of a MED-EP reduced concentrations of circulating TMAO in obese men and women. This study also showed a positive relationship between TMAO concentrations and a clinical marker of insulin resistance. These new findings support clinically relevant metabolic risk implications of TMAO and suggest that lowering red meat consumption in the context of a MED-EP may reduce this risk factor.

7. Peptide YY, a hormone secreted by the gut, increases with the ingestion of wheat high in resistant starch. Dietary fiber has been associated with increased satiety, but different types and sources of fiber vary in their chemical properties and biological effects. Americans fail to consume sufficient fiber and prefer to consume refined wheat, the most common grain in the U.S. diet, but it is low in dietary fiber. A study by ARS researchers in Davis, California, tested baked wheat rolls with high resistant starch (RS) developed by selective breeding and showed that consuming RS rolls compared to rolls with conventional wheat increased peptide YY, a hormone that is known to increase satiety and decrease food intake. Other commercially available forms of resistant starch can be added to food products, but the resistant starch wheat is most amenable to baking and will increase fiber to recommended levels if substituted for regular wheat in baked products. The increase in circulating peptide YY suggests that replacing refined wheat with RS2-enriched wheat in baked products may increase satiety and help prevent unhealthy weight gain due to overeating.

8. Limiting eating to 8 hours a day improves body composition in male endurance athletes. Time restrictive eating (TRE) is a popular diet pattern promoting weight loss and reduction in disease risk for non-athletes, yet this pattern has not been tested in endurance athletes who may benefit by boosting muscle and liver forms of energy necessary for optimal performance. A study by ARS researchers in Davis, California, in collaboration with researchers at University of California, Davis, was conducted to test if TRE led to positive changes in body composition or physical performance compared to a non-restrictive eating pattern. Results indicated that TRE was associated with reduction in body fat mass, without loss of lean body mass. These changes in body composition did not affect performance negatively in a 10-kilometer time trial. For endurance runners, TRE provides the potential benefits of lowered fat mass, maintained lean mass, improved running economy, and reduced energy demands of running at a given velocity, all of which could enhance an athlete’s performance.

9. Weight loss changes an array of short and long-term satiety hormones. Some, but not all research has shown that dairy intake increases weight loss, but little is known about how this might occur. As part of a controlled weight loss trial, ARS researchers in Davis, California, designed a protocol to test if inclusion of dairy products influenced feelings of hunger/fullness along with hormones known to affect appetite. Results showed that the amount of dairy in the controlled diets had little, if any, influence on appetite measures. However, weight loss did increase reported desire-to-eat and the amount of ghrelin, a short-term hunger hormone, and decreased insulin and leptin, both associated with long-term satiety. In this controlled trial, weight loss superseded effects of dairy intake to influence appetite, suggesting that, unfortunately for dieters, signals are in place to return body weight to pre-weight loss levels.

10. Low vitamin A status associated with lower plasma lipids and inflammatory mediators. Low vitamin A (VA) status is common among lactating women in low-income countries. Lactation has substantial effects on a mother’s metabolism and VA is known to be needed in multiple biological processes, including growth, vision, immunity, and reproduction. A pilot study by researchers at the California Polytechnical Institute in San Luis Obispo and the University of California, Davis, in collaboration with ARS researchers in Davis, California, was conducted to assess broad metabolic impacts of low VA status in lactating women. Results indicated that low VA status was associated with lower levels of inflammatory lipid mediators, lipids involved in appetite regulation, and multiple classes of lipids associated with cellular structural integrity. The findings of this pilot study suggest that low VA may fundamentally alter lipid metabolism that may underly some of the known negative impacts on immune function associated with poor status of this nutrient.

11. A meal challenge test reveals borderline metabolic complications in a clinically healthy population. The use of meal challenge tests to assess the responses in carbohydrate and fat metabolism after a meal is well established in clinical nutrition research with implications for metabolic and cardiovascular disease. However, challenge meal compositions and protocols remain variable. ARS researchers in Davis, California, validated the use of a meal challenge test containing palm oil, sucrose, and egg white protein for the parallel determination of insulin sensitivity and triglyceride responses to a meal in a group of more than 325 clinically healthy men and women. The procedure was shown to provide equivalent determinations of insulin sensitivity as from the standard clinical practice of ingesting glucose alone, and allowed the simultaneous determination of triglyceride responses to the meal, providing unique information regarding cardiovascular disease risk. Notably, despite the ingestion of an equivalent amount of fat, two percent of the population showed minimal triglyceride appearance by six hours, while 25 percent had increasing triglycerides through six hours. The developed meal challenge test provides valuable information on the variability of insulin and triglyceride responses to a meal and may identify individuals with pre-emergent cardiometabolic disease.

Review Publications
Dimitratos, S.M., Swartz, J.R., Laugero, K.D. 2022. Pathways of parental influence on adolescent diet and obesity: A physiological stress-focused perspective. Nutrition Reviews. 80(70):1800-1810. Article nuac004. https://doi.org/10.1093/nutrit/nuac004.
Shivakoti, R., Newman, J.W., Hanna, L.E., Queiroz, A.T., Borkowski, K., Gupte, A.N., Paradkar, M., Satyamurthi, P., Kulkarni, V., Selva, M., Pradhan, N., Shivakumar, S.V., Natarajan, S., Karunaianantham, R., Gupte, N., Thiruvengadam, K., Fiehn, O., Bharadwaj, R., Kagal, A., Gaikwad, S., Sangle, S., Golub, J.E., Andrade, B.B., Mave, V., Gupta, A., Padmapriyadarsini, C. 2022. Host lipidome and tuberculosis treatment failure. European Respiratory Journal. 59. Article 2004532. https://doi.org/10.1183/13993003.04532-2020.
Krishnan, S., O'Connor, L., Wang, Y., Gertz, E.R., Campbell, W.W., Bennett, B.J. 2021. Adopting a Mediterranean-style eating pattern with low, but not moderate, unprocessed, lean red meat intake reduces fasting serum trimethylamine N-oxide (TMAO) in adults who are overweight or obese. British Journal of Nutrition. https://doi.org/10.1017/S0007114521004694.
Laugero, K.D., Tryon, M., Mack, C., Caldarone, B., Hanania, T., McGonigle, P., Roland, B., Parkes, D. 2021. Peripherally administered amylin inhibits stress-like behaviors and enhances cognitive performance. Physiology and Behavior. 244. Article 113668. https://doi.org/10.1016/j.physbeh.2021.113668.
Dhillon, J., Newman, J.W., Fiehn, O., Ortiz, R.M. 2022. Almond consumption for 8 weeks altered host and microbial metabolism in comparison to a control snack in young adults. Journal of the American Nutrition Association. Article 2025168. https://doi.org/10.1080/07315724.2021.2025168.
Hughes, R., Horn, W.F., Wen, A., Rust, B., Woodhouse, L.R., Newman, J.W., Keim, N.L. 2021. Resistant starch wheat increases PYY and decreases GIP but has no effect on self-reported perceptions of satiety. Appetite. 168. Article 105802. https://doi.org/10.1016/j.appet.2021.105802.
Young, B.E., Wescott, J., Kemp, J., Allen, L.H., Hampel, D., Garces, A.L., Figueroa, L., Goudar, S.S., Dhaded, S.M., Somannavar, M., Saleem, S., Ali, S.A., Hambridge, M., Krebs, N.F.,The Women First Working Group. 2021. B-vitamins and choline in human milk are not impacted by a preconception lipid-based nutrient supplement, but differ among three low-to-middle income settings – Findings from the women first trial. Frontiers in Nutrition. 8. Article 750680. https://doi.org/10.3389/fnut.2021.750680.
Hampel, D., Shahab-Ferdows, S., Newman, J.W., Allen, L.H. 2021. Improving LC-MS analysis of human milk B-vitamins by lactose removal. Journal of Chromatography B. 1183. Article 122968. https://doi.org/10.1016/j.jchromb.2021.122968.
Bragg, M.G., Prado, E.L., Arnold, C.D., Zyba, S.J., Maleta, K.M., Caswell, B.L., Bennett, B.J., Iannotti, L.L., Lutter, C.K., Stewart, C.P. 2022. Plasma choline concentration was not increased after a 6-month egg intervention among 6-9-month old Malawian children: Results from a randomized controlled trial. Current Developments in Nutrition. 6(2). Article nzab150. https://doi.org/10.1093/cdn/nzab150.
Richardson, C.E., Krishnan, S., Gray, I.J., Keim, N.L., Newman, J.W. 2022. The omega-3 index response to an 8 week randomized intervention containing three fatty fish meals per week is influenced by adiposity in overweight to obese women. Frontiers in Nutrition. 9. Article 810003. https://doi.org/10.3389/fnut.2022.810003.
Mazi, T.A., Borkowski, K., Fiehn, O., Bowlus, C.L., Sarkar, S., Matsukuma, K., Ali, M.R., Kieffer, D.A., Wan, Y.Y., Stanhope, K.L., Havel, P.J., Newman, J.W., Medici, V. 2022. Plasma oxylipin profile discriminates ethnicities in subjects with non-alcoholic steatohepatitis: An exploratory analysis. Metabolites. 12(2). Article 192. https://doi.org/10.3390/metabo12020192.
James, K.L., Gertz, E.R., Cervantes, E., Bonnel, E., Stephensen, C.B., Kable, M.E., Bennett, B.J. 2022. Diet, fecal microbiome, and trimethylamine N-oxide in a cohort of metabolically healthy United States adults. Nutrients. 14(7). Article 1376. https://doi.org/10.3390/nu14071376.
VerHague, M., Albright, J., Barron, K., Kim, M., Bennett, B.J. 2022. Obesogenic and diabetic effects of CD44 in mice are sexually dimorphic and dependent on genetic background. Biology of Sex Differences. 13. Article 14. https://doi.org/10.1186/s13293-022-00426-2.
Yoo, W., Zieba, J.K., Foegeding, N.J., Torres, T.P., Shelton, C.D., Shealy, N.G., Byndloss, A.J., Cevallos, S.A., Gertz, E.R., Tiffany, C.R., Thomas, J., Litvak, Y., Nguyen, H., Olsan, E.E., Bennett, B.J., Rathmell, J.C., Major, A.S., Baumler, A.J., Byndloss, M.X. 2021. High-fat diet–induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide. Science. 373(6556):813-818. https://doi.org/10.1126/science.aba3683.
Krishnan, S., Gertz, E.R., Adams, S.H., Newman, J.W., Pedersen, T.L., Keim, N.L., Bennett, B.J. 2021. Effects of a diet based on the Dietary Guidelines on vascular health and TMAO in women with cardiometabolic risk factors. Nutrition Metabolism and Cardiovascular Disease. 32(1):210-219. https://doi.org/10.1016/j.numecd.2021.09.013.
Batalha, M.A., Ferreira, A.L., Freitas-Costa, N.C., Figueiredo, A.C., Carrilho, T.R., Shahab-Ferdows, S., Hampel, D., Allen, L.H., Perez-Escamilla, R., Kac, G. 2021. Factors associated with longitudinal changes in B-vitamin and choline concentrations of human milk. American Journal of Clinical Nutrition. 114(4):1560-1573. https://doi.org/10.1093/ajcn/nqab191.
Allen, L.H., Hampel, D., Shahab-Ferdows, S., Andersson, M., Barros, E., Doel, A., Eriksen, K.G., Christensen, S., Islam, M., Kac, G., Keya, F.K., Michaelsen, K., Mucci, D., Njie, F., Peerson, J., Moore, S.E. 2021. The mothers, infants, and lactation quality (MILQ) study: A multi-center collaboration. Current Developments in Nutrition. 5(10). Article nzab116. https://doi.org/10.1093/cdn/nzab116.
Artegoitia, V.M., Newman, J.W., Foote, A.P., Shackelford, S.D., King, D.A., Wheeler, T.L., Lewis, R.M., Freetly, H.C. 2022. Non-invasive metabolomics biomarkers of production efficiency and beef carcass quality traits. Scientific Reports. 12. Article 231. https://doi.org/10.1038/s41598-021-04049-2.
Borkowski, K., Pedersen, T.L., Seyfried, N.T., Lah, J.J., Levey, A.I., Hales, C.M., Dammer, E.B., Blach, C., Louie, G., Kaddurah-Daouk, R., Newman, J.W. 2021. Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease. Alzheimer's Research & Therapy. 13. Article 149. https://doi.org/10.1186/s13195-021-00893-6.
Bermingham, K.M., Brennan, L., Segurado, R., Gray, I.J., Barron, R.E., Gibney, E.R., Ryan, M.F., Gibney, M.J., Newman, J.W., O'Sullivan, A.M. 2021. Genetic and environmental influences on serum oxylipins, endocannabinoids, bile acids and steroids. Prostaglandins Leukotrienes and Essential Fatty Acids. 173. Article 102338. https://doi.org/10.1016/j.plefa.2021.102338.
Wright, D.N., Katundu, K.G., Viscarra, J.A., Crocker, D.E., Newman, J.W., La Frano, M.R., Ortiz, R.M. 2021. Oxylipin responses to fasting and insulin infusion in a large mammalian model of fasting-induced insulin resistance, the northern elephant seal. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 321(4):R537-R546. https://doi.org/10.1152/ajpregu.00016.2021.
Artegoitia Etchev, V.M., Krishnan, S., Bonnel, E.L., Stephensen, C.B., Keim, N.L., Newman, J.W. 2021. Healthy eating index patterns in adults by sex and age predict cardiometabolic risk factors in a cross-sectional study. Biomed Central (BMC) Nutrition. 7. Article 30. https://doi.org/10.1186/s40795-021-00432-4.
Sigala, D.M., Hieronimus, B., Medici, V., Lee, V., Nunez, M.V., Bremer, A.A., Cox, C.L., Price, C.A., Benyam, Y., Abdelhafez, Y., Mcgahan, J.P., Keim, N.L., Goran, M., Parcini, G., Tura, A., Sirlin, C.B., Chaudhari, A.J., Havel, P.J., Stanhope, K.L. 2022. The dose-response effects of consuming high fructose corn syrup-sweetened beverages on hepatic lipid content and insulin sensitivity in young adults. Nutrients. 14(8). Article 1648. https://doi.org/10.3390/nu14081648.
Sigala, D.M., Hieronimus, B., Medici, V., Lee, V., Nunez, M.V., Bremer, A.A., Cox, C.L., Price, C.A., Benyam, Y., Chaudhari, A.J., Abdelhafez, Y., McGahan, J.P., Goran, M., Sirlin, C.B., Pacini, G., Tura, A., Keim, N.L., Havel, P.J., Stanhope, K.L. 2021. Consuming sucrose- or HFCS-sweetened beverages increases hepatic lipid and decreases insulin sensitivity in adults. Journal of Clinical Endocrinology and Metabolism. 106(11):3248-3264. https://doi.org/10.1210/clinem/dgab508.
Tovar, A.P., Richardson, C.E., Keim, N.L., Van Loan, M.D., Davis, B., Casazza, G.A. 2021. Four weeks of 16/8 time restrictive feeding in endurance trained male runners decreases fat mass, without affecting exercise performance. Nutrients. 13(9). Article 2941. https://doi.org/10.3390/nu13092941.
Hieronimus, B., Medici, V., Bremer, A.A., Lee, V., Nunez, M.V., Sigala, D.M., Keim, N.L., Havel, P.J., Stanhope, K.L. 2020. Synergistic effects of fructose and glucose on lipoprotein risk factors for cardiovascular disease in young adults. Metabolism. 112. Article 154356. https://doi.org/10.1016/j.metabol.2020.154356.
Sigala, D.M., Widaman, A., Herionimus, B., Nunez, M., Lee, V., Benyam, Y., Bremer, A.A., Medici, V., Havel, P., Stanhope, K.L., Keim, N.L. 2020. Effects of consuming sugar-sweetened beverages for 2 weeks on 24-h circulating leptin profiles, ad libitum food intake and body weight in young adults. Nutrients. 12(2). Article 3893. https://doi.org/10.3390/nu12123893.
Chin, E.L., Van Loan, M., Spearman, S., Bonnel, E.L., Laugero, K.D., Stephensen, C.B., Lemay, D.G. 2021. Machine learning identifies stool pH as predictor of bone mineral density in healthy multiethnic US adults. Journal of Nutrition. 151(11):3379-3390. https://doi.org/10.1093/jn/nxab266.
Soltani, H., Keim, N.L., Laugero, K.D. 2022. Waking salivary cortisol associated with magnitude of cholesterol reduction in women fed a healthy whole-food diet for 8 weeks. Current Developments in Nutrition. 6(5). Article nzac083. https://doi.org/10.1093/cdn/nzac083.
Dimitratos, S., Hercules, M., Stephensen, C.B., Cervantes, E., Laugero, K.D. 2021. Association between physiological stress load and diet quality patterns differs between male and female adults. Physiology and Behavior. 240. Article 113538. https://doi.org/10.1016/j.physbeh.2021.113538.
Borkowski, K., Taha, A.Y., Pedersen, T.L., De Jager, P.L., Bennett, D.A., Arnold, M., Kaddurah-Daouk, R., Newman, J.W. 2021. Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification. Scientific Reports. 11. Article 18964. https://doi.org/10.1038/s41598-021-98640-2.
Borkowski, K., Newman, J.W., Aghaeepour, N., Mayo, J.A., Blazenovic, I., Fiehn, O., Stevenson, D.K., Shaw, G.M., Carmichael, S.L. 2020. Mid-gestation serum lipidomic profile associations with spontaneous preterm birth are influenced by body mass index. PLoS ONE. 15(11). Article e0239115. https://doi.org/10.1371/journal.pone.0239115.
Oliver, A., Xue, Z., Villanueva, Y.T., Durbin-Johnson, B., Alkan, Z., Taft, D.H., Liu, J., Korf, I., Laugero, K.D., Stephensen, C.B., Mills, D.A., Kable, M.E., Lemay, D.G. 2022. Association of diet and antimicrobial resistance in healthy U.S. adults. mBio. 13(3). Article e00101-22. https://doi.org/10.1128/mbio.00101-22.
Tacad, D.K., Tovar, A.P., Richardson, C.E., Horn, W.F., Keim, N.L., Krishnan, G.P., Krishnan, S. 2022. Satiety associated with calorie restriction and time-restricted feeding: Central neuroendocrine integration. Advances in Nutrition. 13(3):758-791. https://doi.org/10.1093/advances/nmac011.
Tacad, D.K., Tovar, A.P., Richardson, C.E., Horn, W.F., Krishnan, G.P., Keim, N.L., Krishnan, S. 2022. Satiety associated with calorie restriction and time-restricted feeding: Peripheral hormones. Advances in Nutrition. 13(3):792-820. https://doi.org/10.1093/advances/nmac014.
Newman, J.W., Krishnan, S., Borkowski, K., Adams, S.H., Stephensen, C.B., Keim, N.L. 2022. Assessing insulin sensitivity and postprandial triglyceridemic response phenotypes with a mixed macronutrient tolerance test. Frontiers in Nutrition. 9. Article 877696. https://doi.org/10.3389/fnut.2022.877696.
Passarelli, S., Free, C.M., Allen, L.H., Batis, C., Beal, T., Biltoft-Jensen, A., Bromage, S., Cao, L., Castellanos-Guttierr, A., Christensen, T., Crispim, S.P., Dekkers, A., De Ridder, K., Kronsteiner-Gicevic, S., Lee, C., Li, Y., Moursi, M., Moyersoen, I., Schmidhuber, J., Shepon, A., Viana, D.F., Golden, C.D. 2022. Estimating national and subnational nutrient intake distributions of global diets. American Journal of Clinical Nutrition. Article nqac108. https://doi.org/10.1093/ajcn/nqac108.
Hinnouho, G., Hampel, D., Shahab-Ferdows, S., Barffour, M.A., McAnena, L., Arnold, C.D., Wessells, K., Kounnavong, S., Allen, L.H., Hess, S.Y. 2022. Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B12 status among young Laotian children: A randomized controlled trial. European Journal of Nutrition. https://doi.org/10.1007/s00394-022-02890-3.
Kim, T., Xie, Y., Li, Q., Artegoitia Etchev, V.M., Lebrilla, C., Keim, N.L., Adams, S., Krishnan, S. 2021. Diet affects glycosylation of serum proteins in women at risk for cardiometabolic disease. European Journal of Nutrition. 60:3727-3741. https://doi.org/10.1007/s00394-021-02539-7.