There is a major resurgence of interest in brown adipose tissue (BAT) biology following the relatively recent discoveries that, contrary to prior belief, BAT does in fact persist into adulthood and appears to play an important, beneficial role in reduced obesity/adiposity risk. The nature of BAT as a specialized heat-producing and energy- expending tissue, its presence in substantial amount in newborns, and its role in neonatal thermogenesis has long been established. However, very little is known about the relationship of BAT characteristics in early life in humans and its implications for obesity/adiposity and metabolic function in subsequent periods of life. Thus, as an important first step to addressing this broad issue, the specific aims of the current proposal are (1) to characterize in a sample of healthy human newborns inter-and intra-individual variation in the volume of BAT at birth and reduction in BAT mass over the first year of life, and (2) to study the associations of BAT mass at birth and BAT mass attrition over the first year of life with key biophysical, metabolic and other developmental parameters, including body composition, total energy expenditure and insulin sensitivity. A unique strength of our proposal is the availability f a cohort of newborns and infants who are extensively characterized over the course of their intrauterine and postnatal life. We are currently conducting NIH-funded prospective, longitudinal projects in a representative, population-based cohort from birth (T1) and over the early postnatal growth phase until 12 months age (T2). These births occur in mothers who, in turn, were extensively and longitudinally studied over the entire course of their index pregnancy. The infant assessments include serial measures of growth, body composition, energy expenditure, and insulin sensitivity, and magnetic resonance imaging (MRI) assessments of the brain during natural sleep. The current R21 proposal seeks funds to incorporate the study of an additional, related outcome of high interest and relevance - newborn and infant brown adipose tissue (BAT) volume - using a non-invasive water-fat separated MRI protocol that our group has validated for the use in human infants. Within the 2-year time frame of the current proposal we propose to assess BAT volume in a subpopulation of N=100 infants longitudinally from birth until 12 months age. Our proposal addresses the following knowledge gaps: a) the developmental ontogeny of brown adipose tissue depots from birth until 12 months age;and b) the consequences and implications of BAT depots in infancy for subsequent obesity risk and associated metabolic dysfunction. The significance and impact of this study derives from the importance of achieving a better understanding of the underlying processes that increase risk or vulnerability for obesity (adiposity) and metabolic dysfunction. This study will collect novel data (serial measures of infant brown adipose tissue mass) and produce results that set the stage for the development of subsequent, testable hypotheses and translational research with important implications for early identification of risk/vulnerable populations, in order to inform the subsequent development of primary and secondary intervention strategies.

Public Health Relevance

Despite the major resurgence of interest in brown adipose tissue (BAT) biology following the recent discoveries that BAT does persist into adulthood and appears to play a beneficial role in reduced obesity/adiposity risk, very little is known about the relationship of BAT characteristics in early life in humans and its implications for obesity/adiposity and metabolic function in subsequent periods of life. The goal of the current proposal is (a) to develop normative human data on brown adipose tissue (BAT) mass in a sample of healthy human infants prospectively assessed over the first year of life using non-invasive water-fat separated Magnetic Resonance Imaging (MRI), and (b) to evaluate to the biophysical and metabolic correlates of BAT mass during the first year of life. The scientific significance of this study is that it will collect novel data (serial measures of infant brown adipse tissue mass) and produce results that set the stage for the development of subsequent, testable hypotheses and translational research. The public health impact is that the information gained from this study will contribute important knowledge that has implications for early identification f risk/vulnerable populations, in order to inform the subsequent development of primary and secondary intervention strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DK098765-02
Application #
8631085
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Laughlin, Maren R
Project Start
2013-04-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
$192,969
Indirect Cost
$67,969
Name
University of California Irvine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697