# Molecular characterization of metabolic reprogramming in anorexia nervosa

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $167,400

## Abstract

PROJECT SUMMARY .
Anorexia nervosa (AN) is a psychiatric illness with the single highest premature mortality rate. Despite this, there
are no robust treatment options for adult patients with AN. In addition, more than 70% of patients relapse within
25 years after treatment creating a chronic course with poor quality of life. The lack of effective therapeutics is
coupled with the lack of molecular mechanisms of AN.
 Recent genomic studies have identified a “metabolic axis” in AN, but the exact role for metabolism is
unclear. Data from acutely weight-restored women with AN (WR-AN) demonstrate significant differences in their
oral glucose tolerance tests (OGTT), lipid profiles, and other metabolism markers compared to age- and weight-
matched healthy control women (HC). Of note, OGTT in WR-AN is highly reactive in clearing the hyperglycemic
peak to return to homeostasis, suggesting that such a bioenergetic efficiency in handling nutrient stressors may
be the basis for relapse in AN. We hypothesized that such systemic differences in metabolism would start with
the molecular building blocks to generate metabolic functional differences in cells of WR-AN vs. HC, which may
be leveraged for novel therapeutics for relapse prevention. Building on our preliminary data, we will test our
hypothesis with 3 research aims: (1) molecular characterization of WR-AN and HC using cellular functional
assays and gene expression analysis, (2) characterization of WR-AN during the first year of weight maintenance
known for its high relapse rates, and (3) ex vivo high-throughput drug and nutrient screening in cellular models
of AN derived from WR-AN. The studies proposed herein will provide the groundwork towards a molecular model
of AN and generate a translational pipeline for precision therapeutics aimed at enhancing science and medicine
for an illness with dismal outcomes, no treatments, and no molecular mechanisms.
 The proposed research will be accompanied by 2 years of mentored training in K99, where the principal
investigator (PI) Dr. Youngjung Kim, MD, PhD, will obtain systematic training in (T1) advanced data science, (T2)
translational science, (T3) comprehensive mastery of clinical trials, (T4) career development, and (T5)
responsible conduct or research. Proposed training plan builds directly on the PI’s physician-scientist training
with experience in molecular experimentation in models of metabolic disorders, clinical research into the
metabolism of AN, and clinical independence as an eating disorder psychiatrist. On this foundation, training will
be guided by a star team of mentors, including: primary mentor Dr. Roy Perlis, MD, MSc; co-mentors Drs.
Madhusmita Misra, MD, MPH and Kamryn Eddy, PhD; advisors Drs. Maurizio Fava, MD and Tom Hildebrandt,
PsyD. With guidance from this exceptional mentoring team, the PI will successfully transition to research
independence by R00 and succeed in building and leading her independent translational research program.

## Key facts

- **NIH application ID:** 10449529
- **Project number:** 1K99MH127366-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Youngjung Kim
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $167,400
- **Award type:** 1
- **Project period:** 2022-08-02 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449529

## Citation

> US National Institutes of Health, RePORTER application 10449529, Molecular characterization of metabolic reprogramming in anorexia nervosa (1K99MH127366-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10449529. Licensed CC0.

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