# Effect of weight loss on intermuscular adipose tissue (IMAT) signaling

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $234,516

## Abstract

Project Summary/Abstract
Black Americans experience disproportionality high rates of obesity, insulin resistance and diabetes and may
derive fewer metabolic benefits from weight loss compared to their White counterparts. The mechanisms
responsible for these differences are poorly understood as Black men and women are typically underrecruited
in clinical studies. Intermuscular adipose tissue (IMAT) is marbled within and next to skeletal muscle and can
cause muscle insulin resistance by bathing the muscles in inflammatory cytokines, adipokines, eicosanoids,
and free fatty acids (the IMAT secretome). The literature shows that Black individuals have greater IMAT
content and adipose tissue inflammation compared to White individuals. Preliminary data show that IMAT has
a similar or worse secretome as visceral adipose tissue towards muscle insulin sensitivity, with secretion of
inflammatory cytokines and eicosanoids contributing to muscle insulin resistance. Our central hypothesis is
that IMAT secretion of inflammatory cytokines is greater in Black than White participants with less improvement
following weight loss, contributing to the racial differences in insulin sensitivity. The purposed research
addresses the critical need to elucidate disease mechanisms in Black individuals by comparing changes in the
IMAT secretome before and after weight loss between Black and White participants. The rationale is that we
will generate new information for differences by race in IMAT paracrine signaling and generate new information
for changes in the IMAT secretome by race after weight loss. By identifying differences between obese Black
and White participants in the IMAT secretome before and after weight loss, this critical research can support
development of tailored diabetes interventions and treatments.
We propose two specific aims: Aim1: Evaluate the potency of IMAT paracrine signaling to decrease insulin
sensitivity in Black and White participants. We hypothesize IMAT secretes greater inflammatory cytokines and
eicosanoids linked to decreased insulin sensitivity in Black compared to White participants. In vitro experiments
will measure the potency of the IMAT secretome to cause insulin resistance by race. Aim 2: Determine the
effect of weight loss on the IMAT content and paracrine signaling in Black versus White participants. We again
hypothesize that weight loss will diminish IMAT secretion of inflammatory cytokines and eicosanoids linked to
decreased insulin sensitivity, but this decrease will be less in Black compared to White individuals. Participants
with obesity will be studied before and after a 12-week weight loss intervention. IMAT will be sampled using an
ultrasound-guided IMAT biopsy technique, insulin sensitivity measured using hyperinsulinemic-euglycemic
clamps, and IMAT content measured using MRI. IMAT will be cultured to generate conditioned media, followed
by conditioned media analyses and testing of its direct metabolic effects in vitro. This...

## Key facts

- **NIH application ID:** 11030655
- **Project number:** 3R01DK134706-02S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** BRYAN C BERGMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,516
- **Award type:** 3
- **Project period:** 2023-07-05 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11030655

## Citation

> US National Institutes of Health, RePORTER application 11030655, Effect of weight loss on intermuscular adipose tissue (IMAT) signaling (3R01DK134706-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11030655. Licensed CC0.

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