# A poly-omic study of the molecular mechanisms underlying maternal diet interventions for offspring obesity and NAFLD

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2021 · $462,254

## Abstract

Project Summary
The demographic shift of populations toward a more obese phenotype in just one or two generations
appears to be primarily attributed to environmental or epigenetic mechanisms. Recent research
advancements have highlighted the importance of nutrition during fetal and early life development and
thus suggest an emerging need to evaluate the impact and risks of maternal diet schemes and understand
the molecular mechanism. Our recent published work reported in a murine model that switching from a
high-fat (HF) diet to a normal-fat (NF) diet 1 week before pregnancy (H1N group) and maintained NF
diet until weaning, was not necessarily beneficial but actually exacerbates the offspring obesity and
glucose intolerance, versus the offspring from the dam on a consistent maternal HF diet (HF group) or NF
diet (NF group) through weaning. In our follow up study, we evaluated the impacts of different durations
of maternal diet transition from a HF to a NF diet, which was 1 week (H1N group), 5 weeks (H5N group)
or 9 weeks (H9N group), before pregnancy, on offspring obesity. We found that a longer transition
duration led to less severe phenotype of obesity and non-alcoholic fatty liver disease (NAFLD). Our
transcriptome data and gene ontology (GO) analysis identified significant association of different
maternal diet-switch regimens with biological process involving lipid metabolism, energy utilization,
epigenetic regulation and one-carbon pool metabolism and one-carbon transfer. Specifically, the DNA
methylation enzymes and the one-carbon pool by folate signaling for methionine cycle was suggested to
be affected by different maternal diet transition regimens. We hypothesize that maternal HF diet and a
short-term transition from a HF to a NF diet genetically upregulate the hepatic lipid profile through
inhibition of DNA methylation associated with disrupted methionine cycle; and a longer term transition
allows restoration of the methionine cycle. To test this hypothesis, we propose to determine that hepatic
lipid profiles are genetically regulated by different maternal diet transition regimens by lipidomics and
signaling pathway analysis on lipid metabolism (Aim1). We will determine that global DNA methylation
was differentially altered by different maternal diet transition regimens which lead to differential
expression of genes involved in lipid metabolism in liver by bisulfite sequencing and an integrative
analysis for identifying lipid metabolism specific DNA methylation by different maternal diet
interventions (Aim2). Lastly, we will determine that disrupted methionine cycle caused by maternal HF
diet contributes to offspring obesity and NAFLD, which is reversed by a long-term, but not a short-term
transition from a HF to a NF diet (Aim3). This proposed study will potentially fill the gap in the field
between lipid metabolism and epigenetics in transgeneration and therefore understand how maternal diet
interventions would affect offspring healt...

## Key facts

- **NIH application ID:** 10137910
- **Project number:** 5R01DK112368-05
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** LingLin Xie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $462,254
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137910

## Citation

> US National Institutes of Health, RePORTER application 10137910, A poly-omic study of the molecular mechanisms underlying maternal diet interventions for offspring obesity and NAFLD (5R01DK112368-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10137910. Licensed CC0.

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