# Effects of Androgen Excess on Lipid Distribution in Congenital Adrenal Hyperplasia

> **NIH NIH R03** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2020 · $91,589

## Abstract

Project Summary
Androgens play an intriguing role in the regulation of body fat distribution, with fundamental differences in
adipose accumulation between males (apple-shaped, android) and females (pear-shaped, gynoid).
Although differences in the abdominal and gluteal-femoral adipose depots have been identified for
endocrine and metabolic function, adipocyte size, and gene regulation of preadipocytes, the mechanisms by
which sex hormones regulate adipose tissue are not fully understood. Females with androgen excess due
to polycystic ovarian syndrome frequently exhibit central obesity, insulin resistance, hepatic steatosis, and
other cardiometabolic risk factors, with similar adverse outcomes that can be seen in female-to-male
transgender individuals receiving testosterone. Congenital adrenal hyperplasia (CAH) due to 21-
hydroxylase deficiency is a condition in which both males and females are exposed to excess androgens as
of the first trimester of pregnancy, and to varying degrees postnatally. One in 15,000 live births are affected
with classical CAH, with universal newborn screening across the U.S. Significant adverse cardiometabolic
outcomes can develop in early childhood and have been identified across the lifespan of CAH individuals,
including obesity, early adiposity rebound, hypertension, and insulin resistance. Yet, there is currently little
in the way of targeted treatment of cardiometabolic risk factors in CAH. The goal of this proposal is to non-
invasively delineate androgen effects on adipose depots and ectopic fat by magnetic resonance (MR)-
based imaging techniques. We propose to perform secondary analyses on imaging studies performed in the
PI’s K23 award. With MR imaging (MRI), we will quantify regional adipose tissue distribution (abdominal
visceral and subcutaneous, and gluteal-femoral) and liver fat, using Dixon quantitative chemical shift
imaging. With proton (1H) MR spectroscopy (MRS), we will examine differences in triglyceride composition
(saturated and unsaturated fatty acids) in abdominal and gluteal-femoral adipose depots, and determine
intra- and extramyocellular lipid content. We hypothesize that we will find an androgen-related, central lipid
distribution (increased abdominal vs. gluteal-femoral), with more saturated fatty acids in abdominal fat, in
CAH youth. We also expect to find increased ectopic fat, and an association with excess androgens, in
CAH. We predict a lack of sex differences in CAH youth, in contrast to sex-matched controls. The specific
aims are to: 1) evaluate abdominal and gluteal-femoral adipose depots for lipid distribution and composition,
non-invasively, by MRI and MRS in CAH youth vs. controls; 2) evaluate ectopic lipid content in liver by MRI
and muscle by MRS in CAH youth vs. controls. This study of a human model of androgen excess can help
to better understand androgen-driven effects on lipid distribution and metabolic risk in both sexes, and may
inform targeted treatments to improve lipid...

## Key facts

- **NIH application ID:** 9958788
- **Project number:** 1R03HD101718-01
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Mimi Susan Kim
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $91,589
- **Award type:** 1
- **Project period:** 2020-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958788

## Citation

> US National Institutes of Health, RePORTER application 9958788, Effects of Androgen Excess on Lipid Distribution in Congenital Adrenal Hyperplasia (1R03HD101718-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9958788. Licensed CC0.

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