Adipose tissue as a key player in obstructive sleep apnoea

Abstract

Obstructive sleep apnoea (OSA) is a major health concern worldwide and adversely affects multiple organs and systems. OSA is associated with obesity in >60% of cases and is independently linked with the development of numerous comorbidities including hypertension, arrhythmia, stroke, coronary heart disease and metabolic dysfunction. The complex interaction between these conditions has a significant impact on patient care and mortality. The pathophysiology of cardiometabolic complications in OSA is still incompletely understood; however, the particular form of intermittent hypoxia (IH) observed in OSA, with repetitive short cycles of desaturation and re-oxygenation, probably plays a pivotal role. There is fast growing evidence that IH mediates some of its detrimental effects through adipose tissue inflammation and dysfunction. This article aims to summarise the effects of IH on adipose tissue in experimental models in a comprehensive way. Data from well-designed controlled trials are also reported with the final goal of proposing new avenues for improving phenotyping and personalised care in OSA.

FIGURE 1

Obesity and intermittent hypoxia (IH) share common mechanistic pathways leading to adipose tissue dysfunction. Healthy adipose tissue contains small adipocytes and anti-inflammatory immune cells (M2 macrophages, T-helper 2 (Th2) cells and regulatory T-cells (T regs)), leading to the production of anti-inflammatory adipokines (interleukin (IL)-10, IL-13, IL-4 and adiponectin). Whereas adipocyte size and number differ between obesity and IH, the molecular alterations are strikingly similar. Indeed, adipocytes from obese and IH exhibit lower oxygen tension levels ([O₂] ↓), increased expression of hypoxia-inducible factor (HIF)-1 and target genes (vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor (PAI)1) and increased oxidative stress and sympathetic activation. In addition, proinflammatory immune cells (CD8⁺ cytotoxic T-cells and Th1 cells) infiltrate the dysfunctional tissue and macrophages polarised to the M1 proinflammatory phenotype. This results in the secretion of proinflammatory adipokines (tumour necrosis factor (TNF)-α, IL-6, IL-1β, monocyte chemotactic protein (MCP)-1, resistin and leptin).

FIGURE 2

Adipose tissue as a key player in systemic consequences of intermittent hypoxia. Physiological consequences of intermittent hypoxia on adipose tissue, the brain, the cardiovascular system, the pancreas, the liver and muscle. Intermittent hypoxia systemic effects may be direct and/or originated through the adipose tissue dysfunction.