# Lifecycle of obesogenic gender behaviors and cardiometabolic disease in women

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2024 · $377,959

## Abstract

Project Summary:
Maternal obesity with increased circulating inflammatory markers can lead to adverse pregnancy outcomes, such
as preeclampsia (PE). Clinical signs of PE include maternal hypertension and proteinuria during the second half
of gestation. Importantly, maternal hypertension only resolves after delivery of the placenta and the fetus, which
is often preterm. The etiology of this is unknown. It is our hypothesis that the maternal gut microbiome as a result
of hyperphagia contributes to heightened inflammation and subsequent abnormal fetoplacental development.
The overarching goal of these proposed studies is to test the hypothesis that maternal hyperphagia-induced
obesity and gut dysbiosis in PE leads to altered short chain fatty acids (SCFA) signaling through embryonic free
fatty acid receptor, GPR43. This in turn contributes to aberrant in utero fetal programming and cardiometabolic
disease. We will test our hypothesis in the BPH/5 mouse model of superimposed PE combining novel in vivo
and ex vivo experiments. In Aim 1, we will determine if the maternal gut microbiome milieu contributes to pro-
inflammatory and/or anti-inflammatory SCFA signaling at the maternal-fetal interface during pregnancy. Also, if
oral supplementation with Lactobacillus (LB) improves PE outcomes in mice with spontaneous PE. NFΚB factors
will be measured in BPH/5+LB and BPH/5 mice depleted of LB. In Aim 2, we will embryo transfer to ascertain
the maternal versus embryonic contribution to SCFA signaling. BPH/5+LB and -LB, and Gpr43-/- embryos will
be transferred to high and low acetate dams. In Aim 3, offspring outcomes will be assessed to determine whether
reversal of maternal obesity via pair-feeding and/or LB+ prevents aberrant fetal cardiac angiogenesis and adult
onset cardiometabolic dysfunction. These experiments will combine the gold standard radiotelemetric blood
pressure recording with metabolic cages to measure cardiometabolic fitness in offspring when maternal gut
dysbiosis is reversed and PE signs are attenuated. These findings will provide groundbreaking prenatal
mechanisms to prevent adult-onset cardiometabolic disease, hypertension, in PE born offspring.

## Key facts

- **NIH application ID:** 10990327
- **Project number:** 1R01HL165467-01A1
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Jennifer Liford Sones
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $377,959
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990327

## Citation

> US National Institutes of Health, RePORTER application 10990327, Lifecycle of obesogenic gender behaviors and cardiometabolic disease in women (1R01HL165467-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10990327. Licensed CC0.

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