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

摘要

Aim: Obstructive sleep apnea-hypopnea syndrome (OSAS) is associated with atherosclerotic cardio-vascular disease. We reported recently daytime hypoadiponectinemia and nocturnal falls in circulating adiponectin concentrations (Δadiponectin) in OSAS patients, in part due to hypoxic stress. The present study investigated the association between Δadiponectin and fat distribution in OSAS males, and the effect of hypoxic stress on adiponectin production in obese yellow-KKAy mice. Methods: The participants in this study were 43 Japanese males who visited the clinic and were newly diagnosed with OSAS. Venous blood samples were collected before sleep and after wakingup. We investigated the effect of hypoxia on adiponectin expression in mesenteric and subcutaneous fat tissues of obese yellow-KKAy mice. We measured adiponectin secretion into media under hypoxic conditions in an ex-vivo model of yellow-KKAy mice. Results: In OSAS males with a relatively higher body mass index (BMI), Δadiponectin correlated inversely with the waist-hip ratio, but not with BMI, waist circumference or hip circumference. In obese yellow-KKAy mice, exposure to hypoxia for 2 days suppressed plasma adiponectin levels, with no apparent change in mesenteric and subcutaneous fat tissue adiponectin mRNA expression. In an ex-vivo study of obese yellow-KKAy mice, hypoxic stress reduced adiponectin in the supernatant of mesenteric fat tissues, but not subcutaneous fat tissues. Conclusions: These findings suggest that abdominal obesity, representing abundant mesenteric fat tissue susceptible to hypoxic stress, partly explains Δadiponectin in OSAS patients, and that reduction of visceral fat accumulation may combat OSAS-related atherosclerotic cardiovascular diseases in abdominal obesity.