# The role of iron in adipose tissue lipolysis, systemic fatty acid mobilization, and insulin resistance in obese humans

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $27,855

## Abstract

SUMMARY
Obesity is associated with the development of insulin resistance and resulting adverse cardiometabolic sequelae.
Elevated fatty acid mobilization from subcutaneous adipose tissue has been identified as a key driver of obesity-
induced insulin resistance; thus, determining mechanisms contributing to elevated fatty acid mobilization in
obesity and examining potential countermeasures to decrease fatty acid mobilization in obese individuals are
critical biomedical research priorities. Epidemiological data indicate that elevated circulating ferritin concentration
(a marker of whole-body iron stores) is associated with the development of insulin resistance, and emerging
evidence indicates that iron homeostasis is altered in obesity. However, the mechanisms linking iron and insulin
resistance remain unclear. My overall working hypothesis is that, in obese humans, high whole-body and adipose
iron levels contribute to elevated systemic fatty acid mobilization, thereby promoting insulin resistance. My novel
preliminary data support the notion that elevated whole-body iron stores are associated with increased lipolytic
activation in adipose tissue, elevated systemic fatty acid mobilization, and insulin resistance in obesity. In the
project proposed in this application, I will expand on these exciting findings by determining the effects of reducing
whole-body iron stores in obese subjects (via blood donation) on factors regulating iron homeostasis and lipolytic
rate in adipose tissue, markers of oxidative stress in adipose tissue, and insulin resistance (Aim 1). Additionally,
I will determine the effects of altering intracellular iron on basal and stimulated lipolytic rate in mature adipocytes
ex vivo and in vitro, and examine the potential role of oxidative stress in mediating the relationship between iron
and lipolysis (Aim 2). By combining these clinical/translational and ex vivo/in vitro studies, the overall findings
from this project will determine the role of iron in the excessive fatty acid mobilization commonly found in obesity,
and whether altered iron homeostasis may represent a key mechanism underlying impairments in metabolic
health. This overall training plan will be overseen by my primary mentor, Dr. Jeffrey Horowitz, an expert in
conducting integrative metabolic studies in humans. Together with the support of collaborating mentors Dr. Yatrik
Shah, an expert in molecular physiology of iron homeostasis, and Dr. Charles Burant, an expert clinician and
metabolism researcher, I am well-positioned to successfully carry out these studies and develop new skills and
expertise that will enable me to pursue a career as an independent scientist investigating interactions between
iron homeostasis and metabolic health.

## Key facts

- **NIH application ID:** 9786058
- **Project number:** 5F32DK117522-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Benjamin Ryan
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $27,855
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-05-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9786058

## Citation

> US National Institutes of Health, RePORTER application 9786058, The role of iron in adipose tissue lipolysis, systemic fatty acid mobilization, and insulin resistance in obese humans (5F32DK117522-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9786058. Licensed CC0.

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