# Impact of Early Life Sodium Intake on Growth and Metabolism – Role of Hypothalamic Mechanisms

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $467,546

## Abstract

Project Summary / Abstract
Postnatal growth failure remains a significant morbidity in very low birth weight infants despite aggressive and
modern parenteral and enteral nutrition practices. Compelling associations have been identified between in-
hospital growth failure and cardiometabolic and neurodevelopmental disorders, heightening the need to further
identify optimal nutritional needs of preterm infants. Studies in animals and humans demonstrate deficiencies in
sodium (Na) supply or intake impair somatic growth. Very low birth weight infants (i) are at increased risk of Na
depletion due to high (and often unappreciated) urine Na loss, (ii) lack osmotically-inactive Na pools that are
normally accrued during late gestation and are likely mobilized after birth to maintain circulating Na pools, and
(iii) demonstrate improved somatic growth when supplied with Na in amounts above that typically provided in
clinical practice. Our objective is to utilize novel animal models and laboratory methodologies to address the
critical lack of understanding of the links between Na homeostasis in early life and metabolic control. The PIs
have generated a wealth of published and preliminary data supporting their hypothesis that insufficient Na in
early life causes programmed changes in short-and long-term energy expenditure via activation of AT1AR/Gαi
signaling in selected hypothalamic neurons. We will address this hypothesis using several new mouse models
to (i) identify the role that osmotically-inactive Na pools and the brain RAS play in metabolic dysfunctions
programmed by Na depletion in early life (Aim 1), and (ii) explore the role of AT1AR signaling within Agouti-related
peptide (AgRP) neurons of the hypothalamic arcuate nucleus in mediating increased energy expenditure &
subsequent growth restriction in mice with Na depletion in early life (Aim 2). We have assembled a research
team with extensive experience with cutting-edge metabolic phenotyping, molecular biology and transgenic
animal production that is uniquely poised to address this clinically relevant issue. Findings from these studies
will greatly increase our mechanistic understanding of the role and importance of early-life Na homeostasis in
growth, metabolism and energy flux and potentially result in paradigm-shifting clinical practices which address
providing sufficient dietary Na to premature infants to optimize a spectrum of long-term outcomes.

## Key facts

- **NIH application ID:** 10862603
- **Project number:** 5R01DK133121-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Justin L Grobe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $467,546
- **Award type:** 5
- **Project period:** 2022-08-12 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862603

## Citation

> US National Institutes of Health, RePORTER application 10862603, Impact of Early Life Sodium Intake on Growth and Metabolism – Role of Hypothalamic Mechanisms (5R01DK133121-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862603. Licensed CC0.

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