Sleep apnea: An overlooked cause of lipotoxicity?

Abstract

Obstructive sleep apnea (OSA) is a common sleep disorder associated with diabetes and cardiovascular disease. However, the mechanisms by which OSA causes cardiometabolic dysfunction are not fully elucidated. OSA increases plasma free fatty acids (FFA) during sleep, reflecting excessive adipose tissue lipolysis. In animal studies, intermittent hypoxia simulating OSA also increases FFA, and the increase is attenuated by beta-adrenergic blockade. In other contexts, excessive plasma FFA can lead to ectopic fat accumulation, insulin resistance, vascular dysfunction, and dyslipidemia. Herein, we propose that OSA is a cause of excessive adipose tissue lipolysis contributing towards systemic “lipotoxicity”. Since visceral and upper-body obesity contributes to OSA pathogenesis, OSA-induced lipolysis may further aggravate the consequences of this metabolically harmful state. If this hypothesis is correct, then OSA may represent a reversible risk factor for cardio-metabolic dysfunction, and this risk might be mitigated by preventing OSA-induced lipolysis during sleep.

The influence of obstructive sleep apnea syndrome on anthropometric parameters at 12 months after laparoscopic sleeve gastrectomy

“…The proposed mechanisms are complex and not fully understood: overstimulation of the sympathetic nervous system, tissue hypoxia, oxidative stress, chronic inflammation and others 32 . A more recent theory describes “lipotoxicity” as a mechanism in which the metabolism of free fatty acids is altered during sleep in patients with OSAS leading to an exaggerated lipolysis, increase in free fatty acids and consequently to a shift in the distribution of adipose tissue from the subcutaneous to visceral site 33 . This pathological mechanism is in line with the recently published results by Dalmar et al 34 .…”

Circulating exosomes and gut microbiome induced insulin resistance in mice exposed to intermittent hypoxia: Effects of physical activity

“…However, pentadecanoic acid is also a FA component of several bacterial cell walls [99] , and the fact that a large proportion of the FA content of feces is not traceable to the diet makes differences in groups receiving the same chow likely attributable to differences in GM-mediated production or release. Alternatively, the increased levels may be due to decreased uptake or even active secretion in to the lumen of the GI tract by the host as a component of the increased lipolysis, circulating free fatty acids (FFAs) [100] , and lipotoxicity associated with IH-induced metabolic dysfunction [101] . Thus, our current work shows both gut microbial and metabolomic content are altered in IH-exposed mice and appear to impair gut function via increases in colonic epithelial permeability, and potentially via bacterial translocation, in light of the IH-induced decreases in tight junction integrity and the increases in LPS plasma levels.…”

MECHANISMS OF ENDOCRINOLOGY: Mechanisms of disease: the endocrinology of obstructive sleep apnoea

“…Furthermore, it is plausible that OSA can lead to weight loss via increased sympathetic activity leading to increased energy expenditure and lipolysis via lipoprotein lipase inhibition and sympathetic activation (62,63). The net effects of the above-mentioned opposing mechanisms/ impacts of weight gain and weight loss is potentially weight maintenance in patients with OSA.…”