# Early Life Fatty Acid Exposures Dictate Obesity Predisposition

> **NIH NIH K01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $151,416

## Abstract

Project Summary and Abstract
 This application is a resubmission for the K01 Career Development Award mentored by Dr. Paul MacLean
and co-mentored by Dr. Jacob Friedman at the University of Colorado Anschutz Medical Campus School of
Medicine. This proposal focuses on elucidating mechanisms established by postnatal fatty acid nutrition that
control adipose development in the neonate. The study design uncouples effects of postnatal nutrition (milk
fatty acids) from fetal fatty acid exposures, and the milk n-6/n-3 PUFA ratio exposures in the young will be
manipulated using a well-characterized transgenic mouse, combined with a basic cross-fostering approach. My
overarching hypothesis is that postnatal exposure to high n-6/n-3 PUFA hypomethylates DNA of
adipogenic pathways, which persists into adulthood to confer adipocyte-intrinsic obesity
predisposition. Lowering the postnatal milk PUFA ratio will reverse postnatal programming, improving
metabolic health later in life. I have integrated my comprehensive training plan with the two novel
approaches designed to test specific effects of postnatal milk PUFA ratio on neonatal adipose development
and function:
Postnatal milk n-6/n-3 PUFA ∆ % DNA methylation in Adipocyte Precursors ∆ Adipose Function
AIM1. Determine the effect of postnatal dietary PUFA ratio on the adipogenic potential of
 adipocyte precursor cells.
AIM2. Determine how altered neonatal dietary PUFA affects adipose tissue development and
function.
I will address gaps in my training by adding targeted didactic and technical skills development, including high-
throughput sequencing analysis, NIDDK tracers workshop, and adipocyte biology workshops, as well as skills
with flow cytometry, DNA methylation, isotope tracers, and metabolic phenotyping. I have recruited a team of
highly productive leaders in the fields of adipose biology and pediatric obesity research, including my mentor
Dr. MacLean and co-mentor Dr. Friedman, adipocyte precursor biology (Drs. Klemm and Rodeheffer),
epigenetics and computational biology (Drs. Yang and Jones), and in mass spectrometry of isotopes and lipid
(Dr. Murphy). This training plan encompasses cutting edge epigenetic analytical tools, an outstanding network
of advisors with considerably expertise, and an innovative experimental approach that facilitate a successful
transition to an independent career as an academic scientist in the developmental origins of obesity.

## Key facts

- **NIH application ID:** 10212714
- **Project number:** 7K01DK109079-04
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Michael C. Rudolph
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $151,416
- **Award type:** 7
- **Project period:** 2020-07-15 → 2022-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212714

## Citation

> US National Institutes of Health, RePORTER application 10212714, Early Life Fatty Acid Exposures Dictate Obesity Predisposition (7K01DK109079-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10212714. Licensed CC0.

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