Metabolic consequences of sleep-disordered breathing.
There is increasing evidence of a causal relationship between sleep-disordered breathing and metabolic dysfunction. Metabolic syndrome (MetS), a cluster of risk factors that promote atherosclerotic cardiovascular disease, comprises central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension, manifestations of altered total body energy regulation. Excess caloric intake is indisputably the key driver of MetS, but other environmental and genetic factors likely play a role; in particular, obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), may induce or exacerbate various aspects of MetS. Clinical studies show that OSA can affect glucose metabolism, cholesterol, inflammatory markers, and nonalcoholic fatty liver disease. Animal models of OSA enable scientists to circumvent confounders such as obesity in clinical studies. In the most widely used model, which involves exposing rodents to IH during their sleep phase, the IH alters circadian glucose homeostasis, impairs muscle carbohydrate uptake, induces hyperlipidemia, and upregulates cholesterol synthesis enzymes. Complicating factors such as obesity or a high-fat diet lead to progressive insulin resistance and liver inflammation, respectively. Mechanisms for these effects are not yet fully understood, but are likely related to energy-conserving adaptations to hypoxia, which is a strong catabolic stressor. Finally, IH may contribute to the morbidity of MetS by inducing inflammation and oxidative stress. Identification of OSA as a potential causative factor in MetS would have immense clinical impact and could improve the management and understanding of both disorders.
Jun
Jonathan
J
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. jjun2@jhmi.edu
Polotsky
Vsevolod Y
VY
D000818:Animals; D050171:Dyslipidemias / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology; D008659:Metabolic Diseases / Q000209:etiology* / Q000503:physiopathology; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D012891:Sleep Apnea Syndromes / Q000150:complications* / Q000503:physiopathology; D012892:Sleep Deprivation / Q000209:etiology / Q000503:physiopathology