# Direct measurement of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme levels in obesity using a novel positron emissiontomography radioligand

> **NIH NIH K01** · YALE UNIVERSITY · 2021 · $153,846

## Abstract

PROJECT SUMMARY
 The prevalence of obesity in the United States population is over 30%, predisposing a large portion of
the population to metabolic diseases. Cortisol, a steroid hormone, is of critical importance in obesity, as it is
responsible for stimulating gluconeogenesis in the liver and promoting adipocyte differentiation and maturation.
Cortisol is activated from cortisone by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-
HSD1).
 The overall aim of this proposal is to examine whole-body 11β-HSD1 enzyme distribution levels during
normal physiology and in response to weight gain, insulin resistance and obesity using the novel 18F-FMOZAT
PET radioligand in rodent and human populations. Whole-body PET imaging can provide a direct measure of
the distribution of 11β-HSD1 allowing comparison to conventional methods using urinary or plasma cortisol
metabolites in both lean and non-diabetic obese human individuals. We propose an obese Zucker fatty (ZF) rat
model that will allow direct in vivo PET imaging of 11β-HSD1 levels in various tissues during progression to
obesity (Aim 1). We also propose to examine 11β-HSD1 levels in lean and non-diabetic obese individuals with
18F-FMOZAT PET to assess tissue-specific variability in whole-body 11β-HSD1 enzyme levels, and compare
these novel direct measures with current methods using urinary metabolites of cortisol (Aim 2).
 The program of research and training described in this K01 Mentored Career Development Award
application will provide the candidate with the requisite skills and experience to become an independent
investigator in the field of endocrinology (obesity). Under the mentorship of field-leading experts in
endocrinology and obesity, and PET imaging, the proposed aims will afford training in the design, conduct and
analysis of novel translational PET imaging techniques to be uniquely applied to metabolic syndromes in
endocrinology, such as obesity. In pursuit of this goal, the candidate proposes to undertake further training in
three primary areas 1) build expertise in clinical endocrinology (obesity) research 2) receive education in the
pathophysiology of obesity and 3) continue to enhance my knowledge of cutting-edge whole-body PET
imaging.
 The opportunities afforded by this award would enable the candidate to embark on a comprehensive,
structured 5-year program of training and research designed to develop an expertise in innovative
endocrinology research methods toward a career as an independent investigator.

## Key facts

- **NIH application ID:** 10197114
- **Project number:** 5K01DK118005-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jason Bini
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $153,846
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197114

## Citation

> US National Institutes of Health, RePORTER application 10197114, Direct measurement of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme levels in obesity using a novel positron emissiontomography radioligand (5K01DK118005-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197114. Licensed CC0.

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