Adipose tissue inflammation by intermittent hypoxia: mechanistic link between obstructive sleep apnoea and metabolic dysfunction

Abstract

Obstructive sleep apnoea (OSA) is a highly prevalent condition and recognized as a major public health burden conveying a significant risk of cardiometabolic diseases and mortality. Type 2 diabetes (T2D), insulin resistance (IR) and glucose tolerance are common in subjects with OSA and this association is at least in part independent of the effects of obesity. Continuous positive airway pressure (CPAP) is the treatment of choice for the majority of patients with OSA but the benefit of CPAP on glycaemic health is uncertain. Thus, a greater understanding of the mechanisms by which OSA leads to metabolic dysfunction might identify novel therapeutic approaches. Intermittent hypoxia (IH), a hallmark feature of OSA, likely plays a key role in the pathogenesis and experimental studies using animal and in vitro models suggest that IH leads to pancreatic β-cell dysfunction and to insulin resistance in the insulin target organs liver, skeletal muscle and adipose tissue. In particular, IH induces a pro-inflammatory phenotype of the visceral adipose tissue with polarization of adipose tissue macrophages towards a M1-pro-inflammatory subtype, upregulation and secretion of numerous pro-inflammatory adipokines and subsequent impairment of the insulin-signalling pathway, changes which bear a striking similarity to adipose tissue dysfunction seen in obesity. In this review, the available evidence linking IH with metabolic dysfunction is explored with a special emphasis on the adipose tissue in this process.

Sleep apnea in relation to metabolism: An urgent need to study underlying mechanisms and to develop novel treatments for this unmet clinical need

“…OSA decreases the uptake of glucose by muscle tissue [47] and may stimulate hypoxia in adipose tissue, leading to inflammation [48,49]. These effects may be mediated by changes in insulin and leptin signaling.…”

Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

“…16 In addition, hypertrophic adipocytes significantly induce local hypoxia, 17 which has also been confirmed to promote AT inflammation via polarizing ATMs to pro-inflammatory subtypes and secreting proinflammatory adipokines. 18 These findings suggest that AT dysfunction is a major source of chronic low-grade inflammation that is associated with the interaction between adipocyte hypertrophy and macrophage infiltration as well as the M1 polarization of ATMs ( Figure 1).…”

Intermittent hypoxia: Friend and foe

“…Intermittent hypoxia is a hallmark feature of obstructive sleep apnoea (OSA), a common sleep disorder that is characterized by recurrent pauses in regular breathing. Numerous findings indicate that hypoxic episodes during OSA may cause pancreatic β‐cell dysfunction and insulin resistance . Similar to the changes seen in obesity, chronic intermittent hypoxia can induce a pro‐inflammatory phenotype of the visceral adipose tissue .…”

“…Similar to the changes seen in obesity, chronic intermittent hypoxia can induce a pro‐inflammatory phenotype of the visceral adipose tissue . There is compelling evidence for an association of OSA with cardiovascular diseases including systemic arterial hypertension, coronary artery disease and heart failure . Therefore, episodic oxygen shortage has been considered as a functional link between metabolic and cardiovascular disorders in OSA.…”