# Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA LINCOLN · 2024 · $915,238

## Abstract

RESEARCH PLAN: PROJECT SUMMARY
GOAL OF THE PARENT AWARD. This administrative supplement is submitted by the Nebraska Center for the
Prevention of Obesity Diseases Through Dietary Molecules (NPOD), currently in Phase 2 COBRE funding at the
University of Nebraska-Lincoln (UNL). NPOD's mission is to prevent, treat, and cure obesity and co-morbidities
by harnessing the power of bioactive food compounds to ameliorate the adverse health effects of obesity. NPOD
Phase 2 is guided by four specific aims: 1) Increase NPOD's critical mass of researchers by hiring five early
career investigators, recruiting new early stage and senior investigators using pilot and seed grant funding, and
continuing to develop strategic alliances with complementary programs; 2) acquire additional equipment for the
research core and formalize experimental design services offered through the administrative core; 3) enhance
the center's mentoring structure and collaborative, multidisciplinary environment; and 4) implement hiring and
recruitment approaches to expand integration of fundamental nutrition and obesity research with clinical,
translational, and community research.
RESEARCH QUESTION FOR THE SUPPLEMENT AWARD. The proposed research will explore whether the selection
of genomic variants in gut bacteria by milk extracellular vesicles (MEVs) alters energy homeostasis in
infants. We have pioneered a novel line of discovery by demonstrating that small extracellular vesicles (sEVs)
and their regulatory cargo do not originate exclusively in endogenous synthesis but may also be absorbed from
milk (milk sEVs, MEVs). Human milk is a rich source of MEVs, and breastfed infants consume approximately
176 trillion MEVs per day. In contrast, formula is essentially free of MEVs and 90% of MEVs are degraded in milk
that was frozen in milk banks or at home due to ice crystal formation. The oral bioavailability of MEVs is
approximately 50% and the portion of MEVs that escapes absorption interacts with the gut microbiome. MEVs
do not only alter bacterial communities, but they also select genomic variants in bacteria where the variants are
transcribed into mRNA and clustered in pathways of energy metabolism (purines, glucose). Other studies are
consistent with these observations and reveal an up to 120-fold increase in purine metabolites in formula-fed
infants and an up to 12.5-fold increase in glucose metabolites in bacteria cultured in media containing a
nutritionally relevant concentration of MEVs compared to MEV-free cultures.
Motivated by these discoveries, we hypothesize that the dietary intake of MEVs alters energy homeostasis in
infants. We will leverage our complementary expertise in bacterial evolution, advanced computational biology,
and the development of innovative “energy sensor” mice to complete three specific aims. In Aim 1, we will assess
the selection of genomic variants in MEV-defined cultures of infant feces. Specifically, we will assess the selection
of genomic variants by...

## Key facts

- **NIH application ID:** 11040110
- **Project number:** 3P20GM104320-10S2
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** JANOS ZEMPLENI
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $915,238
- **Award type:** 3
- **Project period:** 2014-08-05 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11040110

## Citation

> US National Institutes of Health, RePORTER application 11040110, Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules (3P20GM104320-10S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11040110. Licensed CC0.

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