# Mechanisms of exercise effects in obese humans: sex-specific regulation of novel adipose tissue function

> **NIH NIH K23** · JOSLIN DIABETES CENTER · 2022 · $136,445

## Abstract

Project Summary/Abstract
Obesity is a major health crisis and there is a great need to develop new treatments for this disease. Regular
physical activity is crucial for the prevention and treatment of obesity and type 2 diabetes, but the mechanisms
that underlie these effects are not well understood. While exercise training has been extensively studied for its
effect on improving glucose homeostasis and skeletal muscle metabolism, the effects of exercise training on
adipose tissue function are only poorly understood. This is especially the case for obese men and women.
Recently, we have provided evidence using rodent models that exercise training can cause adaptations to
adipose tissue that mediate some of the beneficial effects on exercise on glucose homeostasis. Some of these
benefits may be mediated by novel adipose-derived factors called adipokines. Another putative mediator of the
effects of exercise on adipose tissue metabolism may be the induction of beiging. Beige adipocytes have
increased fuel oxidation and thermogenesis, making beiging a potential therapy for obesity. Our research, along
with others, has clearly shown that exercise training causes scWAT beiging in male rodents, but our more recent
data show that obesity may negate exercise-induced beiging. In addition, we find that exercise training only
increases beiging in male, but not female mice. There have only been limited, or no studies of beiging and novel
exercise-induced adipokines in humans. Thus, the research focus of this career development award is to
determine whether exercise training regulates novel adipokine physiology, circulating factors, and beiging in
obese women and men. The Specific Aims are: 1) To elucidate the effects of obesity on exercise training-
induced regulation of scWAT beiging in human subjects, and to determine if training-induced adaptations to
scWAT are sex-specific; 2) To determine the underlying mechanisms of sex-specific regulation of exercise
training-induced adaptations to scWAT; and 3) To characterize and discover novel exercise-regulated
adipokines, and to identify circulating factors as biomarkers of exercise-induced metabolic changes in lean and
obese men and women. The Principal Investigator on this Career Development Award has a strong
background in exercise physiology and human translational research, but will benefit from additional career
development to transform into a successful, independent investigator. The mentoring committee consists of a
strong multi-disciplinary team of nationally recognized leaders in exercise physiology, adipose tissue biology
and physician-scientists with expertise in human translational physiology. The proposed career development
plan outlines detailed coursework and utilizes the stimulating, resource-rich environments available through the
Joslin Diabetes Center and Harvard University to ensure a successful transition toward independence. By
conducting these studies, working closely with the mentoring com...

## Key facts

- **NIH application ID:** 10667772
- **Project number:** 3K23DK114550-05S1
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** ROELAND J MIDDELBEEK
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $136,445
- **Award type:** 3
- **Project period:** 2018-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667772

## Citation

> US National Institutes of Health, RePORTER application 10667772, Mechanisms of exercise effects in obese humans: sex-specific regulation of novel adipose tissue function (3K23DK114550-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10667772. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*