# Metabolite regulation of adipocyte differentiation in obesity

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2022 · $46,752

## Abstract

ABSTRACT
The triad of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM) affects roughly 33% of U.S. adults
and raises the risk of death from cardiovascular disease. The epidemiological association of obesity with T2DM
is unequivocal, but mechanistic links remain unclear. However, it is clear T2DM is distinctly associated with
defective fat cell (adipocyte) function, particularly energy storage as lipids and secretion of hormones for
systemic insulin sensitivity. We discovered the expression of the enzyme aspartoacylase (ASPA) in white
adipose tissue (WAT) correlates with insulin sensitivity in obese subjects. ASPA governs intracellular acetate
generation and myelin formation in the brain, but its effect in other tissues remains unknown. This
application's overall scientific objective is to unravel how ASPA and acetate contribute to lipid substrates in WAT
using well-established in vitro tools and mouse models of obesity. The central hypothesis is that ASPA-derived
acetate promotes adipocyte differentiation and systemic energy balance. I will test this hypothesis by pursuing
three specific aims: 1) Demonstrate how altered ASPA expression affects lipogenesis in white adipocytes;
2) Define the impact of extracellular acetate on adipogenic competency of precursor cells; 3) Establish the
metabolic effects of ASPA disruption in vivo. Mature adipocytes express high ASPA levels and byproducts of
ASPA activity flow into lipogenesis, nucleotide biosynthesis, and histone modifications. Therefore, ASPA function
likely integrates multiple pathways necessary for adipocytes to overcome nutrient demands in obesity. Lastly,
the mentor and training environment will build research and career development skills to realize my ultimate goal
of becoming an independent scientist.

## Key facts

- **NIH application ID:** 10387771
- **Project number:** 1F31DK130596-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** JESSICA Beserra FELIX
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-02-07 → 2025-02-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387771

## Citation

> US National Institutes of Health, RePORTER application 10387771, Metabolite regulation of adipocyte differentiation in obesity (1F31DK130596-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10387771. Licensed CC0.

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