# Lipolysis during sleep and cardiometabolic consequences of sleep apnea

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $100,911

## Abstract

PROJECT SUMMARY: Lipolysis during Sleep and Cardiometabolic Consequences of Sleep Apnea
Obstructive sleep apnea (OSA) is a common disorder that impairs breathing during sleep. OSA is a risk factor
for type 2 diabetes and cardiovascular disease, leading causes of worldwide death and disability.
Furthermore, OSA can induce insulin resistance, vascular dysfunction, and inflammation – insults that
ultimately lead to diabetes and atherosclerotic cardiovascular disease. Currently, the mechanism by which
OSA causes cardiometabolic dysfunction is not known. This lack of knowledge makes it impossible to
determine which asymptomatic patients require treatment, or to develop protective therapies for those unable
to tolerate continuous positive airway pressure (CPAP) therapy. We contend that this knowledge gap is
caused by lack of attention to the nocturnal sleep period, as nearly all OSA metabolic studies have focused on
morning rather than nocturnal outcomes. Our laboratory discovered dynamic metabolic changes in OSA by
frequently sampling blood during uninterrupted sleep. We used CPAP withdrawal to examine the isolated
metabolic impact of OSA, comparing the same patients on CPAP to their metabolism off CPAP. CPAP
withdrawal dynamically increased nocturnal FFA, glucose, blood pressure, and heart rate compared to CPAP.
Substrate elevations began immediately with sleep onset and persisted during sleep. Excessive stimulation of
adipose tissue lipolysis, can cause “lipotoxicity” resulting in insulin resistance, hyperlipidemia, vascular
dysfunction, and inflammation. Therefore, our overarching hypothesis is that OSA causes excessive SNS
stimulation of lipolysis during sleep which can be prevented by beta adrenergic blockade. In this proposal, we
use CPAP withdrawal, beta adrenergic blockade, and stable isotope techniques to unravel mechanisms and
consequences of OSA-induced metabolic dysfunction during sleep. First, we examine determinants of
nocturnal FFA elevation, including metrics of OSA severity, SNS activity, and patient anthropometric features.
Second, we examine mechanisms of nocturnal FFA elevation with beta blockade and stable isotope
techniques. Third, we examine downstream cardiometabolic consequences of nocturnal FFA elevation. If
successful, we will identify which OSA patients are at risk for cardiometabolic dysfunction, and pave the way
for clinical trials of beta blockade to protect the metabolic health of millions of patients unable or unwilling to
use CPAP.

## Key facts

- **NIH application ID:** 10135268
- **Project number:** 3R01HL135483-03S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jonathan C. Jun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $100,911
- **Award type:** 3
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135268

## Citation

> US National Institutes of Health, RePORTER application 10135268, Lipolysis during sleep and cardiometabolic consequences of sleep apnea (3R01HL135483-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135268. Licensed CC0.

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