# BAT as a therapeutic for the metabolic and cardiac dysfunction with senescence.

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $601,884

## Abstract

PROJECT SUMMARY/ABSTRACT
The US population is rapidly aging. It is projected that by 2030, more than 20% of the population will be over
65 years of age1. Aging is accompanied by increased metabolic and cardiovascular disease. An important
tissue to combat metabolic disease and influence heart function is brown adipose tissue (BAT). Brown
adipose tissue (BAT) is a thermogenic tissue that has a high capacity for both glucose and lipid oxidation,
making BAT a potential target to decrease plasma glucose and lipids and to protect against obesity and it's co-
morbidities, including type 2 diabetes and cardiovascular disease (CVD). Increasing the amount of BAT by
transplantation improves metabolic health, reduces adiposity, and increases glucose uptake into the heart.
BAT has great potential as a therapeutic target to combat both metabolic and cardiovascular disease, but BAT
decreases with age. Thus, we hypothesized that increasing BAT could be a potential therapeutic to improve
the metabolic and cardiovascular impairments that occur with aging. Our preliminary data demonstrate that
transplantation of BAT into an aged mouse (18 months) improves metabolic and cardiovascular health. We
have also generated exciting data showing that exercise increases the signaling lipid 12,13-diHOME from BAT
in humans. 12,13-diHOME is decreased with age in both humans and mice, while exercise in an elderly
population restores 12,13-diHOME to concentrations similar to young adult subjects. Injection of this lipid into
mice has a direct effect on the heart, increasing left ventricular pressure development. Taken together, our
exciting preliminary data show that 1) transplantation of BAT improves metabolic and cardiovascular health in
an aged mouse; 2) exercise-training increases the signaling lipid 12,13-diHOME; 3) concentrations of 12,13-
diHOME are decreased with age in humans and mice; and 4) injection of 12,13-diHOME in mice directly
affects heart function. Here, we will test the novel paradigm that BAT exerts endocrine effects that improves
metabolic health and cardiac function in senescence with three specific aims: 1) Determine the role of BAT on
age-induced impairments in metabolism and insulin sensitivity; 2) Determine the role of BAT on the age-
induced impairments in cardiac function; and 3) Determine if BAT mass and endocrine function is linked with
metabolism or cardiac function in older adults. This project will establish if increasing BAT, and specifically the
lipid 12,13-diHOME, negates the metabolic and cardiovascular impairments that occur with senescence in
rodents and humans. The proposed studies have the potential to elucidate a novel role, and potential
therapeutic approach, for BAT to negate the detrimental effects of aging.
.

## Key facts

- **NIH application ID:** 10355418
- **Project number:** 5R01AG060542-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Paul Martin Coen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $601,884
- **Award type:** 5
- **Project period:** 2019-05-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355418

## Citation

> US National Institutes of Health, RePORTER application 10355418, BAT as a therapeutic for the metabolic and cardiac dysfunction with senescence. (5R01AG060542-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10355418. Licensed CC0.

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