# Effect of surgical and pharmacological obesity treatments on hepatic fat, energy flux, and mitochondria

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2023 · $48,815

## Abstract

PROPOSAL SUMMARY (ABSTRACT)
Research Background and Impact: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease
worldwide and leads to early mortality. Because adolescent NAFLD largely presents as asymptomatic, research
should focus on adolescents at particularly high-risk for disease, which includes those with extreme obesity
and/or polycystic ovary syndrome (PCOS). The only approved treatment for NAFLD is lifestyle intervention, yet
feasibility and long-term maintenance is extremely challenging in youth. Surgical and pharmacological obesity
interventions have been explored for treatment of NAFLD in adults, with emerging data suggesting vertical sleeve
gastrectomy (VSG) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve NAFLD. Data from both
adults and pre-clinical rodent models suggest that aberrant hepatic mitochondria and hepatic energy flux are
critically involved in the pathogenesis of NAFLD, but whether these underlying mechanisms are responsive to
therapy remains unknown. Further, these surgical and pharmacological treatments have not been studied in
youth. Therefore, the goal of this proposal is to use a translational research approach to evaluate hepatic fat,
metabolism, and mitochondrial function before and after surgical (VSG) and pharmacological (GLP1-RA)
interventions in youth (and mice for VSG) at high risk for NAFLD due to obesity and/or PCOS. We will assess
hepatic fat via liver MRI, use oral glycerol isotope tracers and serum and hepatic isotopomer analysis via NMR
to quantify and describe dynamics of hepatic metabolism, and measure mitochondria function via high resolution
respirometry of fresh liver tissue and non-invasive 31Phos-MRS for intrahepatic phosphate concentrations. These
studies will provide excellent mechanistic insight into emerging therapeutic options and will improve the
immediate and long-term health of at-risk youth.
Candidate and Training: My long-term career goal is to be an independent, academic scientist with a translational
research program focused on understanding the molecular signaling events underlying the pathophysiology of
metabolic disease, with a focus on NAFLD. I have extensive experience in pre-clinical mouse models but to
become an independent translational investigator, I need training in clinical trial research. These proposed
studies will expand my research capabilities to include clinical trial implementation, stable isotope tracers, and
31Phos MRS. I will also expand my pre-clinical and bench science research techniques to include mouse survival
surgery and lipidomics. The opportunities provided by my institution (University of Colorado Anschutz Medical
Campus) and by my mentorship team (Drs. Melanie Cree-Green, Darleen Sandoval, Jane Reusch, Craig Malloy,
Bryan Bergman, Laura Pyle) will provide excellent training in integrative hepatic metabolism.

## Key facts

- **NIH application ID:** 10606390
- **Project number:** 1F32DK134122-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kelly Fuller
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $48,815
- **Award type:** 1
- **Project period:** 2023-07-01 → 2024-02-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10606390

## Citation

> US National Institutes of Health, RePORTER application 10606390, Effect of surgical and pharmacological obesity treatments on hepatic fat, energy flux, and mitochondria (1F32DK134122-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10606390. Licensed CC0.

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