# Synergistic effect of maternal insulin-resistance and cortisol in pregnancy on fetal programming of child mitochondrial function and obesity risk

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $246,493

## Abstract

Childhood obesity represents a major public health challenge. Growing evidence supports an 
important role for intrauterine conditions in shaping susceptibility for obesity (the fetal 
origins concept). However, many key questions remain regarding determinants, outcomes and 
underlying mechanisms. First, although maternal metabolic and stress hormones have separately been 
identified as key biological effectors of fetal programming, their interaction has not yet been 
examined in this context. Second, although it’s well established that it is not BMI, per se, 
but excess fat mass and its relative distribution (intra-abdominal, hepatic) that underlies the 
detrimental effects of obesity, it is not yet known whether fetal programming influences the 
distribution of adipose tissue mass. Third, although mitochondrial function-the central 
modulator of cellular energy production, storage and use-has been identified as a key mediator of 
the effects of insulin- resistance (IR) and stress/cortisol on the development and pathogenesis 
of obesity, its role as a putative mechanism in fetal programming has yet to be 
determined. Dr. Lauren Gyllenhammer’s K99/R00 proposal addresses these 3 knowledge 
gaps using complementary designs (observational and experimental), state-of-the-art 
methods (Magnetic Resonance (MR) and Dual Energy X-Ray Absorptiometry (DXA) imaging), and 
multiple levels of analysis (cells to in vivo physiology), to test the hypothesis that maternal 
prenatal stress/cortisol potentiates the unfavorable effects of gestational IR on offspring adipose 
tissue mass/distribution, mediated by offspring mitochondrial function. In the K99 mentored phase, 
Dr. Gyllenhammer will leverage and add measures to an ongoing NIH-funded prenatal observational 
cohort, with existing maternal prenatal cortisol and fasting metabolic measures and offspring 
serial % fat mass measures (DXA from birth to 5yrs) in N=100 mother/child dyads. She will 
add novel measures of MR-based adipose tissue distribution and mitochondrial 
function in the 5 yr old children, and examine the statistical interaction between maternal 
cortisol and fasting markers of IR on these outcomes. She will advance her knowledge of fetal 
programming, gestational/developmental biology, and obtain advanced bench and analysis 
techniques relevant for DOHaD research (cellular biology/mitochondria bench training, 
bioinformatics analysis methods, cutting-edge MRI methods in newborns and young 
children) through investigation of these aims, extensive hands-on training, conferences, 
didactic instruction, and guidance from a diverse advisory committee of respected researchers. In 
the R00 phase, she will enroll a new, independent cohort of N=80 pregnant women and use an 
experimental cross-over study design to quantify the physiological interaction of prenatal stress 
and IR to prospectively predict newborn mitochondrial function and adipose mass and distribution 
trajectory from birth till 6 mo age...

## Key facts

- **NIH application ID:** 10844563
- **Project number:** 5R00HD097302-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Lauren Elizabeth Gyllenhammer
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,493
- **Award type:** 5
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844563

## Citation

> US National Institutes of Health, RePORTER application 10844563, Synergistic effect of maternal insulin-resistance and cortisol in pregnancy on fetal programming of child mitochondrial function and obesity risk (5R00HD097302-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10844563. Licensed CC0.

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