The Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Therapy on Skeletal Muscle Lipid Content in Obese and Nonobese Men.

Obstructive sleep apnea (OSA), independently of obesity (OBS), predisposes to insulin resistance (IR) for largely unknown reasons. Because OSA-related intermittent hypoxia triggers lipolysis, overnight increases in circulating free fatty acids (FFAs) including palmitic acid (PA) may lead to ectopic intramuscular lipid accumulation potentially contributing to IR. Using 3-T-1H-magnetic resonance spectroscopy, we therefore compared intramyocellular and extramyocellular lipid (IMCL and EMCL) in the vastus lateralis muscle at approximately 7 am between 26 male patients with moderate-to-severe OSA (17 obese, 9 nonobese) and 23 healthy male controls (12 obese, 11 nonobese). Fiber type composition was evaluated by muscle biopsies. Moreover, we measured fasted FFAs including PA, glycated hemoglobin A1c, thigh subcutaneous fat volume (ScFAT, 1.5-T magnetic resonance tomography), and maximal oxygen uptake (VO2max). Fourteen patients were reassessed after continuous positive airway pressure (CPAP) therapy. Total FFAs and PA were significantly (by 178% and 166%) higher in OSA patients vs controls and correlated with the apnea-hypopnea index (AHI) (r ≥ 0.45, P < .01). Moreover, IMCL and EMCL were 55% (P < .05) and 40% (P < .05) higher in OSA patients, that is, 114% and 103% in nonobese, 24.4% and 8.4% in obese participants (with higher control levels). Overall, PA, FFAs (minus PA), and ScFAT significantly contributed to IMCL (multiple r = 0.568, P = .002). CPAP significantly decreased EMCL (-26%) and, by trend only, IMCL, total FFAs, and PA. Muscle fiber composition was unaffected by OSA or CPAP. Increases in IMCL and EMCL are detectable at approximately 7 am in OSA patients and are partly attributable to overnight FFA excesses and high ScFAT or body mass index. CPAP decreases FFAs and IMCL by trend but significantly reduces EMCL.

High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h-1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m-2. Fifteen OSA patients were reassessed after 3-5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with "hypoxic stress" (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h-1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.