Abstract
Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific.
Highlights
Mice are a favored animal model to study human diseases as their small size allows for many animals to be kept at relatively low economical costs and because mice are amendable to genetic manipulation (Gordon 2012)
Given the paucity of data on the effects of temperature on blood glucose regulation in mice, we investigate whether acute exposure to temperatures within and below the thermoneutral zone (TNZ) affects glucose tolerance test (GTT) and insulin tolerance test (ITT) in a commonly used mice strain (C57BL/6J)
Initial body mass of the mice used for GTT was 22.4 Æ 0.5 g (n = 20) and 21.7 Æ 0.4 g (n = 20) for the mice used for ITT and respirometry
Summary
Mice are a favored animal model to study human diseases as their small size allows for many animals to be kept at relatively low economical costs and because mice are amendable to genetic manipulation (Gordon 2012). Despite the prevalent use of mice in biomedical research, there is a growing apprehension that captive mice are hypertensive and hyperphagic (e.g., Martin et al 2010) Much of this concern relates to current housing recommendations stipulating that mice must be kept at 20–26°C (NRC 2011), which is well below their thermoneutral zone (TNZ) of approximately 30–32°C (Gordon 2012; Maloney et al 2014). The TNZ of mice is substantially higher than humans due to a high overall heat conductance that primarily stems from the high body surface to volume ratio This implies that mice kept at prescribed temperatures have considerably elevated metabolism with an attending elevation of heart rate (Swoap et al 2008; Feldmann et al 2009; Cannon and Nedergaard 2011).
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