John Newman, Ph.D.

Associate Adjunct Professor, UC Davis Department of Nutrition

Office: (530) 752-1009

Email address: john.newman2@usda.gov

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Research Interests

The Newman laboratory investigates the impact of dietary lipids on process associated with obesity and inflammation, how these effects alter lipid mediator composition of different biological compartment, and how these cumulative changes influence tissue lipid metabolism and signaling to affect physiology. This work is focused by an effort to understand whether fine-tuning an individual's dietary lipid intake can improve body weight and health beyond those recommended to the general population by the Dietary Guidelines for Americans. Moreover, we seek to understand how individual variations in responses to diets and exercise govern the relationship between dietary lipids, lipid mediators and physiological outcomes which influence disease risk and progression.

A major target of our efforts focuses on the measurement of lipids and lipid mediators in experimental models ranging from cell culture, to animal models and human interventions. Lipids constitute a broad assemblage of important molecules in biochemistry, and we are building and implementing platforms to efficiently measure large number of these chemical species using methods commonly referred to as metabolic profiling or targeted metabolomics. Our current tool box allows us to measure the metabolic cascades described at the right.

The regulation of physiological processes are modulated and mediated by metabolites that are produced in the body, and diet, genetics, and health status can alter the formation of these compounds. Among these are the lipid mediators a diverse array of metabolites formed from fatty acids with a wide array of physiological impacts. For instance as shown in the figure below, the metabolism of just one fatty acid, arachidonic acid, can lead to a multitude of products that have major impacts on physiology.

Since the biological responses to dietary lipids often involve the action of bioactive metabolites, too fully understand the mechanisms behind the biological responses to lipids in the diet, we must determine how metabolic products of those lipids change in tissues. To this end we have begun to explore these questions, and are developing novel analytical chemistry approaches to for this purpose. For example, below we show that dietary oils change both the lipid and lipid mediator profiles of tissues in different ways, and the mediators within these two tissues are distributed into different lipid sub compartments.

Importantly, such changes would be expected to have fundamental impacts on the normal function of adipose tissue, as the balance of these and other mediators are important regulators of the functional behavior and response of these cell types to external stimuli like inflammation.

Finally, we are very interested in understanding how these bioactive metabolites are trafficked in the body, and are developing analytical approaches to probe the metabolite profiles within sub-compartments in the blood.

Newman Lab Themes

Improving Public Health by Understanding Diversity in Diet, Body, and Brain Interactions: To refine dietary recommendations and to understand the physiology and pathophysiology of obesity, there is a need to clarify how complex pathways influenced by dietary patterns affect metabolism, behavior, and health outcomes. Importantly, significant person-to-person differences exist with respect to susceptibility to obesity and associated disorders, driven in part by variance in metabolic and behavioral responses to specific environmental factors (i.e., habitual diet, physical activity, stress, and a ‘permissive’ food environment). This work will identify relationships between dietary intake, physical activity, stress, eating behaviors, and metabolic flexibility and encompasses two major WHNRC human phenotyping studies and complementary human, animal model, and in vitro studies.

Individual Metabolism and Physiology Signatures (iMAPS) Study: Understanding how an individual’s metabolism and physiology interact with dietary factors to impact health and health risks is a key to refining how dietary recommendations are developed and delivered to improve the overall health of the American population. In this study, we recruited overweight women with marginal, yet healthy measures of metabolic syndrome risk factors and randomized them to diets either reflecting the typical American diet as determined by the National Health and Nutrition Examination Survey (https://www.cdc.gov/nchs/nhanes/index.htm). Participants remained on these diets for eight weeks. To probe participant metabolic responses to food, and whether those responses changed with time on the diet, individuals were periodically subjected to a mixed nutrient challenge of fat, carbohydrate, and protein, and blood was collected to measure the post-eating (i.e. postprandial) effects on metabolites in their blood. We are measuring factors in the blood which will report on glucose control, liver health, inflammatory status, blood pressure regulation, as well as factors which modulate hunger. The primary goal of this research is to determine how diet quality, in the absence of weight loss, effects metabolic risk factors of the metabolic syndrome.

The WHNRC Cross-sectional Phenotyping Study: Inter-individual variability in responses to dietary factors is poorly understood. To better understand the implications of such variability, we need to first understand the frequency of specific phenotypes within the population, and to determine if these change in association with simple measureable factors including gender, age, and body weight. To address this knowledge gap, a coordinated research effort at the WHNRC will phenotypically characterize 400 individuals ages 18 – 63 in the normal, overweight and obese body mass categories between Sept of 2015 and Oct of 2019. Study participants will have their metabolism perturbed using a mixed macronutrient challenge and the Newman group will be investigating the postprandial metabolic response in circulating lipids and lipid mediators as a phenotyping tool.

Drug-Vitamin Interactions Mediated by the Thiamine Transporter, SLC19A3: It has been discovered that metformin, a common treatment for hyperglycemia associated with diabetes onset, is a substrate for a major transporter of thiamine (i.e. vitamin B1) in the gut. Moreover, rare side effects of metformin are reminiscent of those experienced with thiamine deficiency (e.g. encephalopathy). In collaboration with colleagues at the University of California San Francisco, and Tufts’ University, we will investigate the impact of metformin on thiamine absorption using cell culture, animal, and human clinical studies. Moreover, we will probe the metabolic impacts of thiamine deficiency using metabolomics techniques to fundamentally improve our understanding of the biochemical impact of this key nutrient. The goal of this investigation is to investigate the potential impact of metformin and other thiamine transporter substrates on subclinical thiamine deficiency with relevance to key at risk populations including the elderly.