Location: Dietary Prevention of Obesity-related Disease Research
2018 Annual Report
Objectives
Objective 1: Determine the effect of consuming dietary sources of fat with varied saturation and chain length on the physiological responses of satiety, lipid oxidation, and energy metabolism.
Sub-objective 1A: Determine the acute effects of consuming dietary fats of varied saturation and chain length on satiety, thermogenesis and energy utilization in healthy individuals.
Sub-objective 1B: Determine the chronic effects of consuming dietary fats of varied saturation and chain length on satiety, energy utilization, and body composition.
Objective 2: Determine the role of long chain omega 3 (LCn3) fatty acids in modulating the function of bone cells and the contribution of RANKL/RANK/OPG pathway in obesity-induced changes in bone metabolism in animal and cell models.
Sub-objective 2A1: Define the role of LCn3 in preventing adiposity-induced bone loss.
Sub-objective 2B: Define the optimal ratio of n6/n3 in improving bone quality and quantity in an obesity animal model.
Objective 3: Define the influences of dietary fatty acids and energy balance upon conversion of alpha-linolenic acid (ALA; 18:3n3) to LCn3.
Sub-Objective 3A: Determine the effects of saturated fatty acids (SFA) content upon mechanisms of ALA disposition under eucaloric conditions.
Sub-Objective 3B: Determine the effects of SFA content upon mechanisms of ALA disposition in rodents under hypercaloric conditions.
Objective 4: Define the extent to which consuming rainbow trout bred for elevated LCn3 content reduces CVD risk markers, such as platelet reactivity and related eicosanoids, in people.
Approach
Fat is an essential part of a healthy diet. However, the fatty acid compositions of dietary fats are often overlooked in designing healthy diets. Many Americans consume diets high in saturated fatty acids (SFA) and low in unsaturated fatty acids, including long-chain omega-3 fatty acids (LCn3). This imbalance may contribute to obesity and exacerbate osteoporosis and cardiovascular disease (CVD). The aim of our work is to provide robust data that will inform evidence-based recommendations for the appropriate levels and composition of dietary fats to maintain health and prevent disease. We will accomplish this aim by completing four research objectives that will clarify how the fatty acid profile of dietary fat contributes to health, or conversely, to disease progression. These objectives will use a combination of clinical translational studies in humans and mechanistic studies in rodents and isolated cells. Objective 1 addresses the role of dietary fats in the development of obesity by studying their effects on the modulation of satiety and energy metabolism; Objective 2 addresses the roles of specific fatty acids in preventing bone structure deterioration and promoting bone health in obesity; Objective 3 addresses the impacts of dietary fatty acids and energy balance on LCn3 metabolism; Objective 4 addresses the impact of consuming LCn3-rich rainbow trout on CVD risk markers in humans. We will fulfill these objectives through a combination of clinical translational and mechanistic studies involving human volunteers and rodent models.
Progress Report
Objective 1A. In this clinical trial we are evaluating acute energetic and satiety responses to dietary fat intake in humans. Specifically, we are evaluating the responses to saturated fat, monounsaturated fat, and polyunsaturated fat containing high linoleic acid, high alpha-linolenic acid, or long chain omega-3 fatty acids. Participants are given a test meal and their energetic responses and satiety responses (gut hormones and subjective responses) are determined over 4 hours. Fatty acid binding protein polymorphisms will be used as a covariate in assessing energetic responses to the treatments. The trial is currently near completion with 5 participants yet to be studied. Objective 1B was discontinued prior to participant recruitment due to the scientist retirement.
Objective 2B. An animal study was initiated to define the optimal ratio of n6/n3 fatty acids in improving bone quality and quantity in an obese animal model. Male mice were assigned randomly to 4 treatment groups and fed one of the following diets for 6 months: a normal-fat diet (10% en) or high-fat diets (45% en) with the n-6 fatty acid, linoleic acid, at 9% en, 6% en, and 3% en. The n-3 fatty acid alpha-linolenic acid was kept constant at 1% en in all diets. Body weight, body composition, bone structure, and markers of bone metabolism were measured. The animal study and sample analysis are complete. Results from the study are being prepared for manuscript submission.
As a subordinate project of Objective 2, we analyzed samples collected from a 28-wk single-arm experimental feeding intervention in humans to determine whether high fruit and vegetable intake is beneficial to bone health. Our data indicate that low intake of fruits and vegetables increased the serum bone resorption marker, C-terminal telopeptide of type 1 collagen (CTX), and decreased the serum bone formation marker, bone specific alkaline phosphatase (BAP). High intake of fruits and vegetables decreased the bone resorption marker CTX and increased the bone formation marker BAP. These results support increased consumption of fruits and vegetables at or above federal dietary guidance to improve bone health. This work is published.
Objective 3. We furthered our studies to determine whether the content of dietary saturated fatty acids (SFA), vs the monounsaturated fatty acid oleic acid, decreases the metabolism of the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALA) to longer chain (LC) polyunsaturated fatty acids. We tested the extent to which medium chain (MC) SFA vs LCSFA (palmitic acid and stearic acid) modified obesity-related disease outcomes in mice fed obesogenic diets for 16 weeks. Our data demonstrate that while all animals became obese with both types of SFA sources, the MCSFA-fed animals had better insulin sensitivity and had less fat deposition in the liver. Lipidomic analysis demonstrated elevated indices of LCPUFA content in the blood and liver in animals consuming the LCSFA diet. This work is submitted for publication. We are now testing whether time restricted feeding of the LCSFA diet can be used to increase the LCPUFA indices but limit obesity and its ensuing fatty liver and insulin resistance.
As a subordinate project of Objective 3, we are investigating the impact of dietary ALA depletion upon gene expression during juvenile growth. We demonstrate that lack of dietary ALA during the juvenile growth period substantially depletes n-3 LCPUFA in the brain, liver, and heart in weanling rats. In collaboration with ARS scientists in Clay Center, Nebraska, and Stoneville, Mississippi, we are performing RNAseq analysis on the brain and liver to determine changes in gene expression.
Objective 4. In this clinical trial, we are comparing the efficacy of fish with differing long chain n3 fatty acid contents to reduce cardiovascular disease (CVD) risk markers in obese people with elevated CVD risk. Specifically, we are comparing diploid and triploid farm-raised rainbow trout and tilapia. We are actively recruiting participants for the study. As part of this research, we determined that n-3 LCPUFA fatty acids in human plasma are incorporated into selective phospholipid and triacylglycerol lipid species following intake of n-3 LCPUFA rich marine fish. This work is now published.
As a subordinate project of Objective 4, we are collaborating with the National Center for Cool and Cold Water Aquaculture in Kearneysville, West Virginia, to determine the impact of finishing diet regimens upon the LCPUFA composition of fillet section of farmed rainbow trout. Our data demonstrated that fasting prior to providing the finishing diet does not improve tissue accumulation of long chain omega 3 fatty acids. Our data also indicate that the finishing diet regimen impacts the accretion of LCPUFA in a fillet section specific manner in rainbow trout. This research is published.
We are playing a critical role in the ARS Dairy Grand Challenge team. We have performed analyses for fatty acids and minerals on >450 independent samples. This work required the development of streamlined sample processing and data analysis protocols.
Accomplishments
1. Modeling fatty acid intakes following introduction of high oleic (HO) oils into the food chain. HO oils are being introduced into food production, but HO oils have a reduced content of polyunsaturated fatty acids (PUFA). ARS scientists at Grand Forks, North Dakota, along with an Ohio State University collaborator studied the impact of replacing HO soybean oil and HO canola oil for commodity soybean and canola oils in graded amounts using sophisticated modeling techniques. Data show that elevated levels of HO oil replacement led to increased intake of total monounsaturated fatty acids, especially oleic acid, and decreased intake of total PUFA, particularly the essential fatty acids, linoleic acid (LA) and alpha-linolenic acid (ALA). Replacement of traditional oils with HO oils at 25%-50% may place specific adult age and sex groupings at risk for not meeting the dietary recommendations for LA and ALA.
2. The mineral content of eggs is minimally influenced by the hen rearing environment. There is a public demand for raising hens in alternative, cage-free environments, but we do not know how these different environments impact the nutrient content of the resulting eggs. ARS scientists at Grand Forks, North Dakota, along with a North Carolina State University scientist studied the effect of conventional battery cages, enrichable cage systems, enriched colony housing, café free housing, and free range rearing systems on the mineral content of eggs. While the mineral content of eggs was modified by rearing environment and the age of the hens, the differences in mineral content were small and unlikely to have a substantial impact on human nutrition.
3. Estimation of linoleic acid (LA) intake in the United States. LA is the primary polyunsaturated fatty acid in the U.S. diet and it is an essential fatty acid. ARS scientists at Grand Forks, North Dakota evaluated the trends in LA intake with reported dietary data from the National Health and Nutrition Examination Surveys from 1999-2004. The scientists found that U.S. adults were meeting the intake recommendation of LA and observed a trend of increasing intake of LA in the U.S. overall sub-categories of age, sex, education, race/ethnicity and income-to-poverty ratio. These data are important for monitoring nutrient intake changes in the U.S. population.
4. Energy restriction and mild omega-3 fatty acid loss in juvenile animals reduces expression of protective genes. Undernutrition is a pervasive problem in several regions of the world. Dietary omega-3 fatty acids are considered essential fatty acids and can be deficient in diets that lack sufficient calories. ARS scientists at Grand Forks, North Dakota demonstrated that lack of calories and lack of omega-3 fatty acids reduce the expression of the protective genes termed metallothioneins in the brain and liver. These data are important for those researchers who study childhood nutrition and development particularly with respect to undernutrition in underdeveloped countries.
5. Improving the nutrient content of farmed trout. ARS scientists in Grand Forks, North Dakota and Kearneysville, West Virginia are collaborating to determine the breeding and feeding practices needed to improve the levels of heart healthy omega 3 fatty acids in farmed raised rainbow trout. Scientists demonstrated that fasting prior to providing the finishing diet does not improve tissue accumulation of long chain omega 3 fatty acids in fillets. Scientists also demonstrated that feeding rainbow trout a finishing diet enriched with long chain omega 3 fatty acids increases the omega 3 fatty acid content of trout fillets in a fillet-dependent manner. These findings will benefit fish producers by determining optimum finishing strategies and American consumers that wish to consume foods with an elevated content of long chain omega 3 fatty acids.
6. Identifying molecular environments for heart healthy omega 3 fatty acids in humans. ARS scientists at Grand Forks, North Dakota developed a novel means of characterizing and analyzing lipid biomarkers of omega 3 fatty acids in human plasma. They determined that omega 3 fatty acids in human plasma are incorporated into selective molecular lipid types following intake of omega 3 rich marine fish. This work will assist clinical and basic scientists in improving biomarker analysis for human nutrition and prevention of disease.
7. Caloric restriction combined with exercise is effective in decreasing obesity and improving bone mass. Weight loss can prevent obesity-related chronic disorders but is detrimental to bone health. ARS scientists at Grand Forks, North Dakota, investigated how the degree of dietary caloric restriction with or without exercise affects fat mass, bone mass, and markers of bone turnover in obese rats fed a high-fat diet. Their work demonstrated that a mild, 8% caloric restriction combined with moderate exercise decreases fat mass and prevents bone loss. These findings support the beneficial role of exercise and caloric restriction to improving bone health during weight loss.
8. Increasing consumption of fruits and vegetables improves bone health in people. Data from controlled intervention trials are lacking regarding the effects of fruit and vegetable intake on bone health in people. ARS scientists at Grand Forks, North Dakota analyzed blood markers of bone turnover in response to changes in fruit and vegetable intake in human participants from a controlled feeding intervention study. The results demonstrate that increasing fruit and vegetable intake suppresses bone resorption and increases bone formation. The findings support consumption of fruits and vegetables at or above federal dietary guidance to improve bone health.
Review Publications
Heflin-Morgan, L.E., Anderson, K.E., Johnson, L.K., Raatz, S.K. 2018. Mineral content of eggs differs with hens strain, age and rearing environment. Poultry Science. https://doi.org/10.3382/ps/pey025.
Raatz, S.K., Conrad, Z.S., Jahns, L.A. 2018. Trends in linoleic acid intake in the United States adult population: NHANES 1999-2014. Prostaglandins Leukotrienes and Essential Fatty Acids. 133:23-28. https://doi.org/10.1016/j.plefa.2018.04.006.
Cleveland, B.M., Raatz, S.K., Picklo, M.J. 2018. Deposition and mobilization of lipids varies across the rainbow trout fillet during feed deprivation and transition from plant to fish oil-based diets. Aquaculture. 491:39-49. https://doi.org.10.1016/j.aquaculture.2018.03.012.
Mehus, A.A., Picklo, M.J. 2017. Brian and hepatic Mt mRNA is reduced in response to mild energy restriction and n-3 polyunsaturated fatty acid deficiency in juvenile rats. Nutrients. 9(10):1145-1163. https://doi.org/10.3390/nu9101145.
