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(TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO2 ϭ 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dosedependently increased plasma TG, with levels peaking at FiO2 ϭ 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO2 ϭ 0.10. Plasma catecholamines also increased inversely with FiO2. Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO2 ϭ 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [ 3 H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-␥, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion.lipolysis; lipases; adipose; thermoregulation; metabolism OBSTRUCTIVE SLEEP APNEA (OSA) causes recurrent episodes of asphyxia and intermittent hypoxia (IH) during sleep. Several studies reveal an association between OSA and elevated circulating triglycerides (TG) (16). In some cases, the severity of hypoxia during sleep correlates with the magnitude of increased TG (18, 48). Furthermore, therapy for OSA with continuous positive airway pressure (CPAP) decreases fasting (61) and postprandial TG levels (51); yet, the mechanisms by which OSA affects TG levels are unclear. One possibility is that repetitive IH increases TG levels. Our laboratory has simulated hypoxic desaturations of OSA in mice, exposing them to diurnal IH (60 desaturations/h, 12 h/day). After chronic IH exposure, mice exhibited ϳ40% increases in plasma TG after 5 days (40), with similar elevations persisting after 4 and 12 wk of ongoing IH exposure (32). We have also shown that chronic IH increases TG via two major mechanisms, increased hepatic secretion (39) and decreased lipoprotein clearance (17).Two important questions have not been addressed by chronic IH experiments. First, is chronicity of hypoxia necessary to affect lipid metabolism? Second, is intermittency a necessary factor? Short-term sustained hypoxia in humans (2, 19, 71) and animals (43, 47) also induces hypertriglyceridemia. Surprisingly, no studies have systematically examined the mechanisms by which acute hypoxic exposures elevate TG. It is conceivable that acute sustained hypoxia increases TG via the same mechanisms that we have described for chronic IH. We ther...

Leptin relieves upper airway obstruction in sleep apnea by activating the forebrain, possibly in the dorsomedial hypothalamus. In contrast, leptin upregulates ventilatory control through hindbrain sites of action, possibly in the nucleus of the solitary tract.