Location: Dietary Prevention of Obesity-related Disease Research
2020 Annual Report
Objectives
Objective 1: Determine postprandial lipoprotein and lipidomic responses to time restricted meal patterns in overweight-obese humans and explore variables that modulate these responses.
Objective 2: Define the impact of dietary fats of differing fatty acid composition upon postprandial lipoprotein type and concentrations in healthy humans in response to multiple meals and explore variables that modulate these responses.
Objective 3: Determine the effects of specific foods with differing fatty acid compositions on the lipidomic signatures of postprandial lipoproteins in healthy humans.
Objective 4: Determine the impact of soil management practices on nutritional quality of plant and animal foods produced in the Northern Great Plains.
Objective 5: Investigate whether agricultural production practices of crops important to the Northern Great Plains (e.g. pulses, animals fed local feedstuffs) alter nutritional outcomes important to humans such as (but not limited to) nutrient bioavailability, modulation and connection of soil and animal/human microbiomes, epigenetic alterations, satiety, food reinforcement, and/or alteration of clinical parameters.
Approach
The overarching theme of this project is to investigate determinants of postprandial (PP) metabolism with the goal reducing chronic disease risk. Although many aspects of diet and lifestyle influence metabolic status and disease trajectory during the lifespan, emerging findings suggest that there may be considerable influence of meal frequency and meal timing in disease prevention. Moreover, abundant data point to the role of dietary fat type as a major influence upon cardiovascular disease (CVD) risk trajectory.
PP lipemia, a risk factor for CVD, is a common underpinning mechanism linking meal timing and dietary fat type. Most evaluations of the effect of dietary fats on CVD disease risk rely on measures obtained in the fasting state, but people exist primarily in a PP state. Recently, time restricted eating has gained substantial attention; however, we do not know how this form of meal patterning impacts PP lipemia. As well, few data have examined the compounding effect of multiple meals and fats of different fatty acid composition on PP lipemia. In this work, we will identify the role of dietary patterning and specified dietary fats on PP lipid and lipoprotein metabolism. The novel results of these innovative investigations will provide enhanced understanding of the influence of meal timing and dietary fatty acid composition in optimizing health and will inform evidence-based dietary recommendations. These studies take advantage of our demonstrated expertise in the successful completion of clinical trials combined with our expertise in cutting edge lipidomic analysis.
Progress Report
Objective 3: Scientists in Grand Forks, North Dakota are determining the impact of eating saturated fats vs polyunsaturated fats upon plasma lipoproteins like low-density lipoprotein (LDL) and high-density lipoprotein (HDL) that are associated with cardiovascular disease risk. This research in this objective includes a clinical study coupled with state-of-the-art mass spectrometry analysis of isolated lipoproteins. The clinical study was developed, the Institutional Review Board approval obtained, and the study initiated with two participants out of the 16 needed completing the required treatments. This research will aid in determining how different dietary fats may modify cardiovascular disease risk.
Researchers completed a study that evaluated the acute energetic and satiety responses to dietary fat intake in humans in order to shed light on whether some dietary fats may be helpful to prevent obesity. Specifically, the responses to saturated fat, monounsaturated fat, and polyunsaturated fat, or long chain omega-3 fatty acids were evaluated. Data from this study have been analyzed.
Scientists in Grand Forks, North Dakota, in collaboration with scientists from Canada evaluated how supplementation with long chain n-3 (LCn-3) polyunsaturated fatty acids found in fish oil may benefit some people but not others. This research used state-of-the-art mass spectrometry to analyze for specific lipid molecules that change in the blood after LCn-3 supplementation. This research required the analysis of several hundred samples and led to the development of high-throughput lipidomic methods. Results from this study demonstrate the lipid signatures of people who respond favorably and unfavorably to LCn-3 supplementation. The results have significant clinical impact.
In collaborative research within the unit, ARS scientists in Grand Forks, North Dakota, investigated (1) whether intermittent fasting under obesogenic conditions maintains elevated content of beneficial long chain polyunsaturated fatty acids while preventing insulin resistance and fatty liver, and (2) how lipid metabolism changes with intermittent fasting. The results demonstrated that intermittent fasting in mice has the benefits of blocking fatty liver and insulin resistance but does not elevate long chain polyunsaturated fatty acids content in the liver and blood.
ARS researchers in Grand Forks, North Dakota, are actively participating in the ARS Grand Synergies projects Dairy Agriculture for People and Planet and the Beef Grand Challenge. Scientists are analyzing hundreds of samples from research projects to evaluate how breed and management strategies impact the nutritional quality of milk and beef. This research led to the development of novel, high-throughput analytical techniques and data handling. Data analysis is currently underway. This research will benefit producers and consumers of dairy and beef.
Accomplishments
1. Identified response phenotypes in people supplemented with n-3 fatty acids. Consuming long chain n-3 (LCn-3) polyunsaturated fatty acids like those found in fish such as salmon and tuna or found in fish oil may prevent cardiovascular disease by lowering the blood concentrations of lipids like triglycerides and cholesterol. However, this benefit occurs only in a part of the population. Using state-of-the-art mass spectrometry, ARS researchers in Grand Forks, North Dakota, in collaboration with scientists from Canada analyzed specific blood lipids obtained from a clinical study in which participants were supplemented with 3 g/day of LCn-3 in the form of fish oil capsules over a 6-week period. Researchers found that selective triglyceride molecules are reduced in people who responded positively to treatment vs people who showed no change or even increases in triglycerides. They also observed that in some, but not all, of those study participants who responded positively with a reduction in triglycerides, there was an added benefit of reduced cholesterol in the blood. Given the high use of LCn-3 supplements and LCn-3 enriched foods for prevention of cardiovascular disease, these findings have clinical and nutritional impact.
2. Intermittent fasting prevents obesity and changes lipid metabolism in mice. Intermittent fasting (also known as time restricted feeding) has gained attention as a potential way to reduce body fat gain and to reduce health problems like insulin resistance and fatty liver. In mice, eating a high-fat, obesity-causing diet leads to insulin resistance and fatty liver. However, intake of this obesity-causing diet also leads to increases in long chain polyunsaturated fatty acids (LCPUFA), considered to be beneficial for health. In this work, ARS scientists in Grand Forks, North Dakota, investigated whether intermittent fasting maintains elevated LCPUFA while preventing insulin resistance and fatty liver and how lipid metabolism changes with intermittent fasting. The results demonstrated that intermittent fasting in mice has the benefits of blocking fatty liver and insulin resistance but does not elevate LCPUFA content in the liver and blood. Intermittent fasting creates a separate profile for fat metabolism in mice indicative of positive metabolic adaptations following intermittent fasting diet pattern. This research will benefit health scientists in government, academics, and industry and provide insight into the impact of diet patterning upon health.
Review Publications
Yan, L., Rust, B.M., Picklo, M.J. 2020. Plasma metabolomic changes in mice with time-restricted feeding-attenuated spontaneous metastasis of Lewis lung carcinoma. Anticancer Research. https://doi.org/10.21873/anticanres.14137.
Yan, L., Sundaram, S., Rust, B.M., Picklo, M.J., Bukowski, M.R. 2020. The metabolome of mammary tumors differs from normal mammary glands but is not altered by time-restricted feeding under obesogenic conditions. Anticancer Research. https://doi.org/10.21873/anticanres.14358.
Cao, J.J., Gregoire, B.R., Michelsen, K.G., Picklo, M.J. 2020. Decreasing the dietary ratio of n-6:n-3 polyunsaturated fatty acids by reducing intake of linoleic acid does not prevent adiposity or bone deterioration in obese mice. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa044.
Cao, J.J., Gregoire, B.R., Michelsen, K.G., Picklo, M.J. 2019. Increasing dietary fish oil reduces adiposity and mitigates bone deterioration in growing C57BL/6 mice fed a high-fat diet. Journal of Nutrition. https://doi.org/10.1093/jn/nxz215.
