# Implications of Obstructive Sleep Apnea for Fat Metabolism

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $711,210

## Abstract

ABSTRACT
Untreated obstructive sleep apnea (OSA) is a precursor for several cardio-metabolic complications including
hypertension, insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Despite advancements
made in identifying an independent association between OSA and metabolic dysfunction, underlying
mechanisms that explicate the association remain elusive. It is well established that intermittent hypoxemia
and recurrent arousals, the two pathognomonic features of OSA, can activate the sympathetic nervous system,
increase oxidative stress, and heighten systemic inflammation. Our preliminary data indicate that alterations in
fat metabolism may also have a fundamental role in the causal chain between OSA and impairments in
glucose homeostasis. Thus, the overarching objective of this proposal is to characterize aberrations in fat
metabolism in OSA. To accomplish this objective, we will employ a combination of exceptionally unique
methods for metabolic phenotyping and determine the putative roles of fat metabolism, skeletal and adipose
tissue enzymatic activity, and toll-like receptor (TLR) signaling as mediators of metabolic dysfunction in OSA.
Moreover, we will examine whether activity of several key skeletal muscle enzymes involved in -oxidation
such as acyl-CoA synthase (ACS), carnitine palmitoyltransferase-1 (CPT-1), -hydroxyacyl-CoA
dehydrogenase (β-HAD) and citrate synthase (CS) are altered in OSA. Finally, we propose to examine
whether OSA interferes with extracellular triglyceride hydrolysis by decreasing the activity of lipoprotein lipase
(LPL), which regulates FFA supply in various tissues for either storage or oxidation. The following two specific
aims are proposed. Aim 1: To assess whether, independent of age, sex, race, and obesity, OSA severity is
associated with alterations in: (1) whole body lipolysis and free fatty acid (FFA) oxidation; (2) subcutaneous
adipose tissue lipolysis; (3) activity of skeletal muscle enzymes (ACS, CPT-1, -HAD, and CS) and TLR2/TLR4
expression; and (4) LPL activity in skeletal muscle and adipose tissue. Aim 2: To determine whether treatment
of OSA with positive airway pressure (PAP) therapy will have salutary effects on: (1) whole body lipolysis and
FFA oxidation; (2) subcutaneous adipose tissue lipolysis; (3) activity of skeletal muscle enzymes (ACS, CPT-1,
-HAD, and CS) and TLR2/TLR4 expression; and (4) LPL activity in skeletal muscle and adipose tissue.
Completion of these aims will add much needed mechanistic insight on how OSA alters glucose and fat
metabolism and help open new therapeutic strategies (i.e., interruption of lipolysis) that could curtail the
metabolic burden imposed by OSA particularly in those that are unable to use PAP therapy.

## Key facts

- **NIH application ID:** 10487577
- **Project number:** 5R01HL146709-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Naresh M Punjabi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $711,210
- **Award type:** 5
- **Project period:** 2021-01-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487577

## Citation

> US National Institutes of Health, RePORTER application 10487577, Implications of Obstructive Sleep Apnea for Fat Metabolism (5R01HL146709-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10487577. Licensed CC0.

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