# Investigation of the preadipocyte primary cilia signalosome

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $40,207

## Abstract

Consequences associated with obesity can be miƟgated by shiŌing adipose Ɵssue expansion from hypertrophic to
hyperplasƟc expansion; the former increases overall size of exisƟng adipocytes and correlates with increased
inflammaƟon, insulin insensiƟvity, and fibrosis, while the laƩer differenƟates new adipocytes from resident
preadipocytes through adipogenesis. Remedying the expansion of our adipose Ɵssue to favor healthier hyperplasƟc
expansion is of the upmost importance to combat the obesity epidemic, as western diets high in fat and carbohydrates
have shown to shiŌ the balance of fat expansion to the more consequenƟal hypertrophic expansion. All preadipocytes
have primary cilia, which are criƟcal for their differenƟaƟon into mature adipocytes. These organelles are typically rich in
signaling components, specifically G protein‐coupled receptors (GPCRs), though liƩle is known about ciliary protein
composiƟon in preadipocytes. Thus far only one receptor has been discovered in the cilium of preadipocytes, and its
acƟvaƟon increases ciliary cAMP and subsequent adipogenesis. Increases in cellular cAMP are necessary for ex vivo
adipogenesis, but it is unknown what role compartmentalized ciliary cAMP has in adipogenesis, though ciliary cAMP in
other cell types has been shown to have differenƟal funcƟons than whole cell cAMP. I hypothesize that cAMP in the
cilium is necessary and sufficient to induce adipogenesis in preadipocytes, and that a suite of ciliary GPCRs acts to
influence this process in a cilia‐dependent manner. My first aim will define the role of ciliary cAMP in adipogenesis, using
chemogeneƟc and optogeneƟc tools to control the generaƟon or depleƟon of ciliary cAMP during adipogenesis to define
its sufficiency and necessity in preadipocyte differenƟaƟon. My second aim will idenƟfy GPCRs that localize to
preadipocyte cilia and invesƟgate their physiological roles in adipose expansion and prevalence in healthy versus
unhealthy adipose Ɵssues.
This work will be conducted at the University of Utah under the guidance of my sponsor, Dr. Keren Hilgendorf, and co‐
sponsor, Dr. Jeremy Reiter, both of whom specialize in ciliary signaling. My thesis commiƩee is composed of
interdisciplinary researchers with a range of specialƟes all pertaining to different porƟons of this proposal, such adipose
Ɵssue, signaling metabolites, GPCRs, and primary cilia signaling. Together, these mentors will provide expert guidance in
all facets of this project. In addiƟon, this project will be supported by the work of mulƟple university core faciliƟes,
including those that offer services in cellular microscopy, flow cytometry, mass spectrometry, and metabolomics. These
faciliƟes offer excellent support and training services to facilitate my growth as a researcher. The training plan presented
was developed to ulƟmately prepare me for a future in academia as an independent researcher in the field of ciliary
signaling and cell fate determinaƟon. In addiƟon to the technical skills this project...

## Key facts

- **NIH application ID:** 10903151
- **Project number:** 1F31DK139738-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Mark David Lee
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,207
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903151

## Citation

> US National Institutes of Health, RePORTER application 10903151, Investigation of the preadipocyte primary cilia signalosome (1F31DK139738-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10903151. Licensed CC0.

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