Location: Microbiome and Metabolism Research
Project Number: 6026-10700-001-022-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jun 2, 2024
End Date: May 30, 2029
Objective:
1. Determine how parental diet quality and metabolic status during critical windows of development programs offspring cardiometabolic health from infancy through adolescence.
1.A. To determine the role of parental energy balance in programing offspring growth, development, and metabolic function across the life span.
1.B. To determine the impact of parental environment (diet, housing temperature etc.) prior to and during gestation on offspring adipose tissue development.
1.C. To examine the influence of parental environment on developmental programming of offspring vascular function and cardiovascular outcomes.
2. Identify specific mechanisms by which prenatal and postnatal fruit and vegetable (FV) consumption program musculoskeletal development (Component 4, PS 4A, PS 4B; Component 5, PS 5A and 5B).
2. A. Define the effects of maternal high fat diet (HFD) and FV intake on offspring bone bioenergetics (mitochondrial function), bone development, and long-term maintenance.
2.B. Investigate the epigenetic regulations by which prenatal and postnatal fruit and vegetable (FV) consumption ameliorates high fat diet-induced skeletal deterioration.
2.C. Define the relative contributions of maternal and postnatal FV rich diet on offspring skeletal muscle health.
3. Investigate the mechanisms by which early feeding patterns, including introduction of solid foods into dietary patterns, work to regulate gut barrier development.
1. Determine how parental diet quality and metabolic status during critical windows of development programs offspring cardiometabolic health from infancy through adolescence.
1.A. To determine the role of parental energy balance in programing offspring growth, development, and metabolic function across the life span.
1.B. To determine the impact of parental environment (diet, housing temperature etc.) prior to and during gestation on offspring adipose tissue development.
1.C. To examine the influence of parental environment on developmental programming of offspring vascular function and cardiovascular outcomes.
2. Identify specific mechanisms by which prenatal and postnatal fruit and vegetable (FV) consumption program musculoskeletal development (Component 4, PS 4A, PS 4B; Component 5, PS 5A and 5B).
2. A. Define the effects of maternal high fat diet (HFD) and FV intake on offspring bone bioenergetics (mitochondrial function), bone development, and long-term maintenance.
2.B. Investigate the epigenetic regulations by which prenatal and postnatal fruit and vegetable (FV) consumption ameliorates high fat diet-induced skeletal deterioration.
2.C. Define the relative contributions of maternal and postnatal FV rich diet on offspring skeletal muscle health.
3. Investigate the mechanisms by which early feeding patterns, including introduction of solid foods into dietary patterns, work to regulate gut barrier development.
Approach:
The risk of obesity, cardiometabolic, and musculoskeletal disease are subject to programming beginning at conception. However, there is a gap in knowledge about how parental nutritional status and metabolism interact with developmental windows to influence offspring risk for obesity and cardiometabolic disease. Insights into specific mechanisms by which fruits and vegetables (FV) may modify cardiometabolic health, musculoskeletal development, and gut health in children and during critical windows of development remains unknown. Objective 1 will use rodent models of parental hypermetabolism to investigate mechanisms driving programming of offspring adipose tissue development, vascular function, and bioenergetics from birth through adolescence. We will use indirect calorimetry to assess offspring energy expenditure and fuel utilization, omics methods to assess genome-wide epigenetic changes in preadipocytes and vascular cells, and longitudinal assessments of blood pressure in conscious free-moving rodents. In Objective 2 we will determine if maternal or postnatal FV consumption (indicative of higher diet quality) rescues the deleterious effects of maternal obesogenic diet on offspring musculoskeletal development. Bone mitochondrial energetics, genome wide DNA methylation and histone modifications in bone cells, skeletal muscle composition/function, and skeletal muscle and bone-specific knockout mouse models will be used to assess the interaction between bone health and skeletal muscle health. Objective 3 will use in vitro and in vivo methods to identify mechanisms by which dietary metabolites derived from solid foods common in early feeding regulate gut barrier development. The effect of solid food introduction on gut barrier integrity will be assessed using both in vitro and rodent models with diets formulated with typical first solid foods during weaning. Studies here will yield an understanding of the mechanisms by which parental energy expenditure and specific bioactive food components derived from healthy diet patterns promote offspring cardiometabolic, musculoskeletal, and gut health. Research from these studies will provide new insights into dietary strategies for the early prevention of obesity, cardiovascular disease, bone disorders, and type 2 diabetes.
