# Adipocyte metabolism and stem cell lineage responses

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $327,500

## Abstract

Project Summary:
Nutrients affect tissue stem cell lineages in all organisms. Interorgan signaling allows the impact of diet or
physiological factors on one organ to be communicated to stem cell lineages elsewhere. Circulating levels of
most energy substrates and metabolites vary with diet, and many of these activate G protein coupled receptors
(GPCRs), which are associated with metabolic diseases, cancers and other disorders. It is therefore essential
to investigate how GPCR signaling links metabolism to stem lineage processes in vivo. Adipocytes have key
metabolic roles, and obesity increases the risk for many diseases. Among them are cancers, which share
similarities with stem cells. Signaling pathways that control normal stem cells are often deregulated in cancers
(e.g. diet-dependent pathways), and cancers and stem cells have large proliferative potential and generate
differentiated cells in deregulated or controlled ways, respectively. The goal of this proposal is to study how
diet controls adipocyte metabolism and how GPCR signaling mediates its effects on stem cell lineages using
the Drosophila germline stem cell (GSC) model. Drosophila has highly conserved adipocyte metabolism and
well characterized stem cells. One can readily identify GSCs and quantify self-renewal, proliferation,
differentiation and survival along their lineage. GSCs and their progeny divide and grow faster on a rich diet,
partially via insulin, steroid hormone, and Target of Rapamycin (TOR) signaling in the ovary. Adipocytes
contribute to the GSC response to diet, as adipocyte-specific disruption of amino acid transport or TOR causes
distinct GSC lineage phenotypes. Our unpublished data show that diet also regulates metabolic pathways in
adipocytes, and key adipocyte enzymes influence GSC number, proliferation, and differentiation, survival of
their daughters. In addition, our results show that distinct G proteins regulate GSC fate and division, and
progeny survival, suggesting that GPCR signaling actively modulates the GSC lineage. We will test our
hypothesis that key diet-dependent metabolic pathways in adipocytes control the levels of metabolites (or other
downstream factors) that act directly on the ovary (or indirectly, through intermediate organs) to modulate the
GSC lineage through the following aims: 1) To determine how macronutrients and diet-dependent hormones
impact key adipocyte metabolic pathways; and 2) To probe the role of G protein coupled receptor (GPCR)
signaling in the GSC lineage. Relevance: Obesity is prevalent in the western world and results in the abnormal
function of fat cells, which in turn increases the risk for many diseases, including cancers. We propose to take
advantage of powerful research tools in fruitflies to investigate how metabolic processes in fat cells normally
generate signals that affect the function of stem cells in other parts of the body. Because of the high degree of
evolutionary conservation of molecules and biological pr...

## Key facts

- **NIH application ID:** 10004144
- **Project number:** 5R01GM125121-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Daniela Drummond-Barbosa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,500
- **Award type:** 5
- **Project period:** 2017-09-05 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004144

## Citation

> US National Institutes of Health, RePORTER application 10004144, Adipocyte metabolism and stem cell lineage responses (5R01GM125121-04). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10004144. Licensed CC0.

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