Location: Obesity and Metabolism Research
Project Number: 2032-51530-025-000-D
Project Type: In-House Appropriated
Start Date: Mar 16, 2019
End Date: Mar 15, 2024
Objective:
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.
