# Maternal obesity, AMPK and Developmental Programming

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2022 · $377,108

## Abstract

Maternal obesity, AMPK and Developmental Programming
 Over 30% of pregnant American women are obese and an additional 30% are over-weight, conditions which
negatively affect fetal development with long-term consequences for offspring health, including pre-disposition
to obesity and type 2 diabetes (T2D). The underlying mechanisms remain poorly defined. Skeletal muscle (SM)
accounts for >30% body weight and is a key tissue for the oxidation of fatty acids and glucose, as is brown
adipose tissue (BAT). Under the support of our previous award, we demonstrated that maternal obesity (MO)
elicits early onset of fibrotic and fatty infiltration (FFI) in offspring SM and BAT, which impairs their functions
and programs metabolic disorders in offspring. We found that AMP-activated protein kinase (AMPK), a known
target for metformin, is robustly inhibited due to MO, correlates with FFI and worsened offspring SM/BAT
functions. In the early embryo, both myogenic and fibrogenic cells are derived from progenitor cells (PCs) in
the dermomyotome. While the embryonic myogenic cells are the sources of both myogenic and brown
adipogenic cells, embryonic fibrogenic cells are sources of fibrogenic and white adipogenic cells in offspring
SM/BAT. Because of this, our previous studies point to embryonic origins for developmental abnormalities of
offspring SM/BAT due to MO, but this is yet to be examined. Using single cell RNA sequencing (scRNA-seq),
we found that embryonic myogenesis is attenuated in E9.5 MO embryos. We hypothesize that MO suppresses
AMPK, which inhibits myogenic commitment and drives uncommitted PCs to fibrogenesis during embryonic
development, programming FFI in offspring SM/BAT. Accordingly, we have three specific aims: 1) Study AMPK
inhibition due to MO in impairing embryonic myogenic commitment; 2) Evaluate AMPK in linking MO to
enhanced embryonic fibrogenesis; and 3) Analyze AMPK as a target for improving embryonic SM/BAT
development of MO and the resulting offspring SM/BAT functions. We will use single cell “omics” for analyzing
embryonic tissues, and embryoid body culture for mechanistic exploration. Knowledge obtained will identify
molecular targets for therapeutics to improve embryonic SM/BAT development and subsequent metabolic
health of MO offspring, helping the increasing populations of obese mothers to deliver healthy children.

## Key facts

- **NIH application ID:** 10535287
- **Project number:** 2R01HD067449-11
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** MIN DU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $377,108
- **Award type:** 2
- **Project period:** 2010-09-27 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535287

## Citation

> US National Institutes of Health, RePORTER application 10535287, Maternal obesity, AMPK and Developmental Programming (2R01HD067449-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10535287. Licensed CC0.

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