# The Impact of Obesity on Somatotrope Function

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2023 · $572,437

## Abstract

SUMMARY
The prevalence of extreme obesity in adults is increasing precipitously and today more than one-third (39.8%)
of adults are obese. Furthermore, the obese condition is characterized by responses and hormone levels that
encourage the accumulation of more fat. Obese individuals are resistant to the appetite suppressing actions of
leptin and to glucose regulation by leptin and they secrete reduced levels of the lipolytic hormone, growth
hormone (GH) from anterior pituitary (AP) somatotropes. There are significant gaps in knowledge about
mechanisms behind the suppression in GH secretion. In light of the importance of somatotropes as metabolic
sensors and the need for their production of GH, there is a critical need to improve our understanding of
somatotrope responses to the stress of obesity. Like all AP cells, somatotropes display plasticity as they are
remodeled to meet fluctuating hormonal and gender-specific needs of the body. Leptin may directly modulate
somatotrope plasticity, although mechanisms are unknown. Furthermore, the impact of leptin is broad in that
it impacts AP cell maturation. The long-term goal of this laboratory is to elucidate the mechanisms by which
AP cells are regulated in order to respond appropriately to metabolic signals. The specific objectives with the
studies described in this application are to determine the mechanisms by which leptin signals somatotropes,
including the identification of gene expression changes and remodeling that occurs under conditions of diet
induced obesity (DIO). This proposed study will test the central hypothesis that the obese state causes sex-
specific somatotrope dysfunction and compromises responses to environmental stresses. A
secondary hypothesis is that post-transcriptional regulation plays a key role in facilitating AP
remodeling. Aim 1 studies will determine the impact of obesity and recovery to normal weight
on somatotrope remodeling and plasticity. Mice will be subject to diet-induced obesity (DIO) under
thermoneutral conditions and a second cohort of animals will recover normal weight after DIO. Unbiased and
targeted approaches including miRNA sequencing (miRNA-seq), single cell RNA-sequencing (scRNA-seq) and
multiplex protein assays will identify signaling pathway mediators and AP cellular response patterns. Aim 2
studies will ascertain the impact of obesity on somatotrope responses to stress. DIO mice will be
challenged with hypothermia and responses assessed by miRNA-seq and scRNA-seq. Aim 2 will also test the
impact of DIO and environmental stress on mice lacking the translational regulatory protein, Musashi in
somatotropes. This study addresses the biological mechanisms regulating energy balance at the level of the AP
and will clarify how somatotropes are remodeled to respond to the metabolic stress of obesity in a sex-specific
manner. The introduction of targeted and unbiased state-of-the-art technologies presents a unique opportunity
for broader mechanistic insights th...

## Key facts

- **NIH application ID:** 10656317
- **Project number:** 5R01DK127723-03
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** GWEN V CHILDS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $572,437
- **Award type:** 5
- **Project period:** 2021-07-17 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656317

## Citation

> US National Institutes of Health, RePORTER application 10656317, The Impact of Obesity on Somatotrope Function (5R01DK127723-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10656317. Licensed CC0.

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