Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes

Reinke C, Bevans-Fonti S, Drager LF, Shin MK, Polotsky VY. Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes. J Appl Physiol 111: 881-890, 2011. First published July 7, 2011; doi: 10.1152/japplphysiol.00492.2011.-Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both obesity and OSA are associated with insulin resistance and systemic inflammation, which may be attributable to tissue hypoxia. We hypothesized that a pattern of hypoxic exposure determines both oxygen profiles in peripheral tissues and systemic metabolic outcomes, and that obesity has a modifying effect. Lean and obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60) [inspired O-2 fraction (FIO2) 21-5%, 60/h], IH 12 times/h (FIO2 5% for 15 s, 12/h), sustained hypoxia (SH; FIO2 10%), or normoxia while fasting. Tissue oxygen partial pressure (PtiO(2)) in liver, skeletal muscle and epididymal fat, plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis factor-alpha (TNF-alpha) were measured. In lean mice, IH60 caused oxygen swings in the liver, whereas fluctuations of PtiO(2) were attenuated in muscle and abolished in fat. In obese mice, baseline liver PtiO(2) was lower than in lean mice, whereas muscle and fat PtiO(2) did not differ. During IH, PtiO(2) was similar in obese and lean mice. All hypoxic regimens caused insulin resistance. In lean mice, hypoxia significantly increased leptin, especially during SH (44-fold); IH60, but not SH, induced a 2.5-to 3-fold increase in TNF-alpha secretion by fat. Obesity was associated with striking increases in leptin and TNF-alpha, which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens.