Aqp5-/- mice exhibit reduced maximal body O2 consumption under cold exposure, normal pulmonary gas exchange, and impaired formation of brown adipose tissue.

The fundamental body functions that determine maximal O₂ uptake (V_O2max) have not been studied in Aqp5^-/- mice (aquaporin 5, AQP5). We measured V_O2max to globally assess these functions and then investigated why it was found altered in Aqp5^-/- mice. V_O2max was measured by the Helox technique, which elicits maximal metabolic rate by intense cold exposure of the animals. We found V_O2max reduced in Aqp5^-/- mice by 20%-30% compared with wild-type (WT) mice. As AQP5 has been implicated to act as a membrane channel for respiratory gases, we studied whether this is caused by the known lack of AQP5 in the alveolar epithelial membranes of Aqp5^-/- mice. Lung function parameters as well as arterial O₂ saturation were normal and identical between Aqp5^-/- and WT mice, indicating that AQP5 does not contribute to pulmonary O₂ exchange. The cause for the decreased V_O2max thus might be found in decreased O₂ consumption of an intensely O₂-consuming peripheral organ such as activated brown adipose tissue (BAT). We found indeed that absence of AQP5 greatly reduces the amount of interscapular BAT formed in response to 4 wk of cold exposure, from 63% in WT to 25% in Aqp5^-/- animals. We conclude that lack of AQP5 does not affect pulmonary O₂ exchange, but greatly inhibits transformation of white to brown adipose tissue. As under cold exposure, BAT is a major source of the animals' heat production, reduction of BAT likely causes the decrease in V_O2max under this condition. [ABSTRACT FROM AUTHOR]