# Early Life n-3 Fatty Acids Increase Novel Adipogenesis-Regulatory Cells to Condition Adipogenesis in a NR2F2 Dependent Manner

> **NIH NIH R03** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $108,750

## Abstract

ABSTRACT
 Nearly 20% of children are obese or overweight. It is anticipated half of childhood obesity will occur by age 5
and more than half of existing children will develop obesity by age 35. Maternal diet-derived nutritional signals
transmitted during perinatal development condition metabolic responses later in life. We found high n-6 to n-3
(n6/n3) fatty acid exposures positively associate with increased infant body fat accumulation; and in mice,
lowering n6/n3 exposure conditioned neonatal adipogenesis epigenetically, imparting long-lasting metabolic
benefit to adults. Our findings led to the central hypothesis:
 Low n6/n3 exposure during development conditions adipogenesis via cellular and functional
 responses within stem-like adipocyte precursor populations.
 Adipocyte precursor cell (APC) subtypes include progenitors, preadipocytes, and newly discovered
“Adipogenesis-regulatory” cells (Areg). Aregs attenuate adipose tissue expansion (ATE) in a cell number
and paracrine way. Importantly, we observe attenuated neonatal body fat accumulation, morphology, and
cellularity from low n6/n3 exposure in mice. This phenotype supports that patterning of ATE is sensitive to early
life n6/n3, yet, the APC subtype frequencies and molecular diversity regulated by low n6/n3 stimuli remain
unknown.
 We began addressing this gap by isolating primary APCs from fat depots of pups with high and low n6/n3
exposure. Preliminary bulk RNA-seq analysis identified increased Areg subtype markers from low n6/n3
exposure. Included is NR2F2 -a key transcriptional regulator linked to attenuated adipogenesis. In co-culture,
APCs conditioned in vivo by low n6/n3 proliferated slower and differentiated less. These findings suggest
increases Areg cell number (or their activity) might attenuate detrimental ATE in neonates.
 This proposal combines state-of-the-art single cell RNA-sequencing, modern flow cytometry techniques,
genetic manipulation of n6/n3 ratios and NR2F2, real-time live cell imaging, and in vitro primary APC culture to
achieve two primary objectives:
 SA1. To quantify Areg cell number simultaneously with Areg specific mRNA signatures triggered by
 high and low n6/n3 postnatal exposures.
 SA2. To determine if NR2F2 mediates the low n6/n3 dependent effect on in vivo adipogenesis, APC
 populations, and APC adipogenic potential.
Impact. Defining molecular responses and cellular diversity of APC subtypes that can condition early life ATE in
vivo could help inform new modalities of obesity prevention.

## Key facts

- **NIH application ID:** 10108364
- **Project number:** 7R03DK122189-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Michael C. Rudolph
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $108,750
- **Award type:** 7
- **Project period:** 2019-08-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108364

## Citation

> US National Institutes of Health, RePORTER application 10108364, Early Life n-3 Fatty Acids Increase Novel Adipogenesis-Regulatory Cells to Condition Adipogenesis in a NR2F2 Dependent Manner (7R03DK122189-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10108364. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*