# Maternal obesity and cardiometabolic health in the offspring

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $606,213

## Abstract

Obesity is a global health problem, leading to increased risk for cardiovascular disease, diabetes, and related
complications. Additionally, the offspring of obese and overweight women are more likely than those born to
normal-weight women to be obese at one year of age; to have metabolic syndrome, hypertension, and liver
disease as young children; and to have cardiovascular disease as adults. The mechanisms of maternal
programming of cardiac impairment in the offspring are unclear, preventing development of strategies to
prevent them. We have developed a mouse model in which maternal high fat/high sucrose (HF/HS) diet-induced obesity
leads to cardiac abnormalities in the offspring. Specifically, despite eating a standard diet after weaning, adult
female F1 offspring of female mice (F0) fed a HF/HS diet developed significantly impaired left ventricular
function as defined by decreased fractional shortening and increased left ventricular inner diameter.
Our objectives here are to determine the extent to which they are inherited transgenerationally and the
mechanism by which these effects occur. Our rationale is if we can determine the mechanism responsible for
this maternal programming of cardiac impairment, we may be able to develop therapeutic measures to prevent
this debilitating mitochondrial dysfunction. We hypothesize that this mitochondrial phenotype leading to the perturbation of cardiac function is transgenerational since it is transmitted by the oocyte. We anticipate that this phenomenon is due to
epigenetic changes to either the nuclear or mitochondrial DNA (mtDNA). We also hypothesize that intra-oocyte
ROS accumulation and/or lipid accumulation are responsible for the epigenetic transmission and are the direct
result of maternal HF/HS diet. The three aims are designed to test these hypotheses. The results of these
studies will provide a clear mechanism to explain the transmission, which will lead to new therapeutic targets.
It is our goal that this work will result in novel preventative measures and potentially pharmacological products
to improve the health of the next generation.

## Key facts

- **NIH application ID:** 10206245
- **Project number:** 5R01HL143431-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Abhinav Diwan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $606,213
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206245

## Citation

> US National Institutes of Health, RePORTER application 10206245, Maternal obesity and cardiometabolic health in the offspring (5R01HL143431-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10206245. Licensed CC0.

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