title: 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 +/- 2.9 vs. 8.8 +/- 5.6 microg/ml (P < 0.05); after wake-up: 5.2 +/- 2.6 vs. 8.5 +/- 5.5 microg/ml (P < 0.01), respectively; means +/- SD]. Serum adiponectin levels diminished significantly during sleep in severe OSAHS patients (P < 0.0001), but one-night nCPAP improved the drop in serum adiponectin levels [-18.4 +/- 13.4% vs. -10.4 +/- 12.4% (P < 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 OSAHS-related diseases during sleep.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 B-5, Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Mina
authors.initials: M
authors.lastname: Sonoda
authors.forename: Ayumu
authors.initials: A
authors.lastname: Hirata
authors.forename: Atsutaka
authors.initials: A
authors.lastname: Yasui
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yoshida
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000328:Adult; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D045422:Continuous Positive Airway Pressure; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin