Nocturnal reduction in circulating adiponectin concentrations related to hypoxic stress in severe obstructive sleep apnea-hypopnea syndrome

Abstract

Previous reports demonstrated that adiponectin has antiatherosclerotic properties. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is reported to exacerbate atherosclerotic diseases. We investigated nocturnal alternation of serum adiponectin levels before sleep and after wake-up in OSAHS patients and the effect of sustained hypoxia on adiponectin in vivo and in vitro. We measured serum adiponectin concentrations in 75 OSAHS patients and 18 control subjects before sleep and after wake-up and examined the effect of one-night nasal continuous positive airway pressure (nCPAP) on adiponectin in 24 severe OSAHS patients. We investigated the effects of hypoxia on adiponectin in mice and cultured adipocytes with a sustained hypoxia model. Circulating adiponectin levels before sleep and after wake-up were lower in severe OSAHS patients than in control subjects [before sleep: 5.9 Ϯ 2.9 vs. 8.8 Ϯ 5.6 g/ml (P Ͻ 0.05); after wake-up: 5.2 Ϯ 2.6 vs. 8.5 Ϯ 5.5 g/ml (P Ͻ 0.01), respectively; means Ϯ SD]. Serum adiponectin levels diminished significantly during sleep in severe OSAHS patients (P Ͻ 0.0001), but one-night nCPAP improved the drop in serum adiponectin levels [Ϫ18.4 Ϯ 13.4% vs. Ϫ10.4 Ϯ 12.4% (P Ͻ 0.05)]. In C57BL/6J mice and 3T3-L1 adipocytes, hypoxic exposure decreased adiponectin concentrations by inhibiting adiponectin regulatory mechanisms at secretion and transcriptional levels. The present study demonstrates nocturnal reduction in circulating adiponectin levels in severe OSAHS. Our experimental studies showed that hypoxic stress induced adiponectin dysregulation at transcriptional and posttranscriptional levels. Hypoxic stress is, at least partly, responsible for the reduction of serum adiponectin in severe OSAHS. Nocturnal reduction in adiponectin in severe OSAHS may be an important risk for cardiovascular events or other OSAHSrelated diseases during sleep. nasal continuous positive airway pressure RECENT STUDIES HAVE DEMONSTRATED that adipose tissue is not only a passive reservoir for energy storage but also produces and secretes a variety of bioactive molecules called adipocytokines, including adiponectin (1a, 20), tumor necrosis factor-␣, leptin, and plasminogen activator inhibitor type 1 (PAI-1) (36). Dysregulated production of adipocytokines is associated with the pathophysiology of obesity-related diseases (1a, 9, 27). The biological functions of adiponectin, which we identified as an adipocytokine in the human adipose cDNA library (20), include improvement of glucose (21) and lipid metabolism (26), prevention of inflammation (31) and atherosclerosis (24), and cardiovascular protection (14,30,38). Serum adiponectin levels are low in visceral obesity (1a), insulin resistance (10), type 2 diabetes (9), and cardiovascular diseases (29). Previous studies demonstrated the possible association between visceral obesity and obstructive sleep apnea-hypopnea syndrome (OSAHS) (39,40). More recent studies reported that obese subjects with OSAHS had hypoadiponectinemia (36,46).In patients with OSAHS, repetitive noctu...

Effect of Continuous Positive Airway Pressure on Adiponectin in Patients With Obstructive Sleep Apnea: A Meta-analysis

“…As a noninvasive treatment of OSA, CPAP therapy could significantly reverse OSA associated hypoxia, sleep fragmentation, sympathetic activation and all these factors contribute to reduced adiponectin in OSA patients [18,35,36]. Thus, it is academically rational that CPAP therapy, to some extent, could increase adiponectin levels.…”

Nocturnal Falls of Adiponectin Levels in Sleep Apnea with Abdominal Obesity and Impact of Hypoxia-Induced Dysregulated Adiponectin Production in Obese Murine Mesenteric Adipose Tissue

“…We demonstrated previously the association between visceral obesity and OSAS 8) . We recently reported daytime hypoadiponectinemia and nocturnal falls in circulating adiponectin concentrations ( adiponectin) in severe OSAS patients, presumably due to hypoxic stress 9) , possibly that might be associated with nocturnal cardiac events. The association between fat distribution and adiponectin in OSAS patients remains unclear.…”

Pathophysiology in Type 2 Diabetes – Type 2 Diabetes and Sleep-Disordered Breathing/Sleep Apnea – Role of Adipocytokines

“…These changes are probably the major underlying mechanisms of lifestylerelated diseases [Kishida, 2011]. Daytime hypoadiponectinemia and nocturnal falls in circulating adiponectin concentrations in OSA patients with abdominal obesity, are in part, due to hypoxic stress [Nakagawa, 2008[Nakagawa, & 2011. A high frequency of SDB was identified in Japanese patients with poorly controlled T2DM, who also had intra-abdominal obesity with nocturnal dysregulated production of adiponectin [Kashine, 2010].…”