# Biobehavioral and Environmental Contributions to Metabolomic Profiles and Early Life Body Composition

> **NIH NIH K99** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $135,054

## Abstract

ABSTRACT: Childhood obesity is a significant public health problem and key risk factor for chronic conditions
in adulthood. As such, there is critical need to understand childhood obesity etiology and identify opportunities
for the earliest possible interventions to promote wellness across the lifespan. To that end, the objective of this
proposal is to use metabolomics to better understand the foundations of variation in adiposity and body
composition (e.g., fat mass, lean mass, bone mass, weight-for-age) in infancy and early life. The long-term
training goal of this project is to support Dr. Heinsberg in becoming an independent investigator with a program
of research dedicated to understanding and preventing obesity and improving maternal/child health. The
mentored K99 will focus on participants from the nation of Samoa, as Pacific Islanders have the highest risk of
obesity-related complications in the world, are one of the fastest-growing U.S. populations, but are
underrepresented in health research. In Pacific Islander adults, a missense variant (rs373863828) in CREB3
Regulatory Factor (CREBRF) has an effect on body mass index larger than any other common variant.
Paradoxically, the obesity-risk allele is protective against diabetes, making its functional role unclear and
necessitating further mechanistic study before intervention can be considered. The obesity phenotypes of the
variant are not present at birth but present clinically later in childhood. Given the results of CREBRF pre-clinical
modeling and our preliminary work in infants, we hypothesize that the biological effects of the variant are
present much earlier in life. To investigate this hypothesis, the K99 will draw from the Foafoaga o le Ola
(“Beginning of Life”) Samoan infant cohort study. Existing resources include infant CREBRF genotype data,
biospecimens, and body composition measured using dual-energy X-ray absorptiometry as well as rich
behavioral/environmental data for mother-infant dyads at 1 week, 4 months, and 20 months post-birth. We will
use temporal, untargeted metabolomics to increase our understanding of the biochemical mechanisms of the
CREBRF variant with an emphasis on behavior/environment (Aim 1) and the foundations of body composition
over the first two years of life (Aim 2). The results are expected to provide knowledge that can be translated to
improved child wellness and health equity in Samoa and Pacific Islander communities in the U.S. With access
to existing biospecimens and rich data from a geographically isolated birth cohort, unparalleled mentorship,
and superb resources, the training environment is truly outstanding. K99 training goals to support the transition
to independence include (1) metabolomic data collection/analysis, (2) metabolomic data interpretation in obese
phenotypes, (3) conduct of childhood obesity research in underrepresented groups, and (4) career
development. In the R00, the K99 methods will be applied to study early life adiposity ...

## Key facts

- **NIH application ID:** 10519784
- **Project number:** 1K99HD107030-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Lacey W Heinsberg
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $135,054
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519784

## Citation

> US National Institutes of Health, RePORTER application 10519784, Biobehavioral and Environmental Contributions to Metabolomic Profiles and Early Life Body Composition (1K99HD107030-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10519784. Licensed CC0.

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