Tissue Partitioning in Early Childhood
Condition: Changes in Bone Mineral Content; Changes in Bone Marrow Adipose Tissue
Study type: Observational

Summary: 
      Early childhood (~4-6 years of age) is an important window for determining body composition
      trajectory and may be a critical period for the development of tissue partitioning patterns
      that influence later disease risk, including obesity and type 2 diabetes. As adiposity
      accelerates during this critical period, deposition/ preservation of fat stores may be
      sustained at the 'expense' of other tissues; i.e. energy homeostasis may be inherently biased
      toward fat gain. The type and amount of tissue mass accrued in early childhood has
      implications for metabolic profile, glucose/insulin homeostasis, hormone profile and resting
      energy expenditure.

      The interplay between fat and bone deposition represents a physiologic trait enabling the
      body to choose between shuttling 'energy' towards accrual of a particular tissue. Plausibly
      the phenotype underlying obesity and diabetes risk may be determined by the differentiation
      of cell type (adipocyte, osteocyte, etc.) during this early stage of growth and development.
      In vitro studies demonstrate transdifferentiation under the influence of specific external
      stimuli, which can switch phenotypes toward other cell lineages. Further, rodent models have
      demonstrated that exposure to stimuli (exercise) early in life may prevent excess fat mass
      accrual in adulthood, even when the stimulus is later removed (animals are no longer
      exercising). Children's early experiences (engagement in physical activity) may
      'environmentally induce' alterations in body composition and predispose individuals to
      diabetes throughout life (Figure 1).

      Hypotheses and Specific Aims: Early growth patterns and cell differentiation may induce long
      term effects on body composition by impacting biological and hormonal axes that regulate
      childhood body composition. Body composition comprises not only absolute mass, but also
      aspects of size, shape and location. To that end, the following specific aims will be
      evaluated:

        1. Quantify body composition, adipose tissue distribution, and relative tissue ratios using
           magnetic resonance imaging (MRI) and dual-energy x-ray absorptiometry (DXA).

             1. Hypothesis: Early partitioning of 'resources' toward fat mass accrual will lead to
                decreased gains in bone mass that may persist long-term.

             2. Hypothesis: Partitioning of tissue toward fat at the expense of bone mass (and
                indirectly, lean mass) will result in adverse effects on glucose/insulin
                metabolism, total energy expenditure, resting metabolic rate and hormone signaling.

             3. Hypothesis: Children with greater levels of physical activity (energy expenditure)
                will have greater partitioning towards bone (and lean) mass.

        2. Quantify adipose tissue distribution and adipocyte cell size and number using MRI and
           histological techniques.

             1. Hypothesis: A relatively greater amount of bone marrow adipose tissue will be
                apparent in those children with low levels of physical activity, resulting in the
                preferential differentiation of pluripotent stem cells towards adipocytes vs
                osteocytes in the bone marrow cavity.

             2. A relatively greater adipocyte cell number will be apparent in those children with
                low levels of physical activity indicating greater differentiation of MSC towards
                adipocytes vs osteocytes.
    


Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Healthy children aged three to seven years
      
Biospecimen description: 
      Samples will be labeled with the study protocol number, a unique identifier, and the date of
      collection.

      Blood specimens will be obtained by the nursing staff at the PCIR. The PCIR processing lab
      will process the samples, which will then be stored in a locked freezer at -80oC in the
      restricted access CNRU Metabolism Core lab (WEBB 337).
    
Keywords: body composition; fat distribution; exercise; diet