# Exercise effects on adipose tissue morphology, metabolic function, and metabolic health with weight loss and weight regain in obesity

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $612,138

## Abstract

Project Summary/Abstract
The combination of caloric restriction and exercise is the most common first-line treatment for obesity-related
disorders, yet we know very little about the synergistic effects of these two very different treatments. A deeper
understanding about mechanisms underlying the health benefits of adding exercise to a weight loss program is
critical for optimizing modifiable components of lifestyle interventions (e.g., exercise intensity). Importantly,
although a reduction in adipose tissue mass is the fundamental adaptation to weight loss, we know almost
nothing about the effects that adding exercise may have on structural and functional changes within adipose
tissue. This is very important because many obesity-related metabolic health complications are tightly linked with
abnormalities in abdominal subcutaneous adipose tissue (aSAT). In particular, high rates of fatty acid release
from aSAT, which is very common in obesity, leads to ectopic lipid deposition in liver, visceral adipose tissue,
and skeletal muscle, and is a major factor underlying insulin resistance. Therefore, increasing the capacity of
aSAT to store and sequester fatty acids will protect against these abnormalities. Importantly, increased capacity
of aSAT to store fat does not translate to increased body fat mass, this requires an energy surplus. Based on
our exciting preliminary findings, we hypothesize exercise triggers key signaling pathways in aSAT to reprogram
the regulation of angiogenesis, adipogenesis, and extracellular matrix (ECM) fibrosis to remodel aSAT for more
effective energy storage. We contend these exercise-induced modifications in aSAT will impart persistent health
benefits even if some weight is regained after weight loss. Finally, although high-intensity interval training (HIIT)
is known to induce robust cardio-metabolic improvements in adults with obesity, little known about the metabolic
impact of adding HIIT to a weight loss program. Comparing HIIT vs. more “conventional” moderate-intensity
continuous training (MICT) will provide important insights to optimize exercise protocols for adults with obesity.
General study design: Obese adults will be randomized to: 1) MICT, 2) HIIT or 3) no exercise (NoEX) - while
they all undergo a standardized calorie restricted diet until they lose 10% body weight. After losing 10% body
weight, all subjects will enter a 6-month follow-up phase (no diet or exercise requirements). Because long-term
adaptations to training largely stem from the accrual of responses to each exercise session, in Aim #1, we will
assess changes in signaling events involved in regulating aSAT angiogenesis, adipogenesis, ECM remodeling,
and inflammatory pathways, during the 24 hours after a session of exercise (HIIT and MICT). In Aim #2, we will
determine the effects of adding exercise training (MICT or HIIT) to a calorie-restricted weight-loss program on
changes in aSAT morphology (e.g., capillarization, ECM fibrotic content and co...

## Key facts

- **NIH application ID:** 10877093
- **Project number:** 5R01DK131724-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jeffrey F Horowitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $612,138
- **Award type:** 5
- **Project period:** 2022-08-16 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877093

## Citation

> US National Institutes of Health, RePORTER application 10877093, Exercise effects on adipose tissue morphology, metabolic function, and metabolic health with weight loss and weight regain in obesity (5R01DK131724-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10877093. Licensed CC0.

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