MiPsummer Programme pdf - Mitochondrial Physiology Society

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Abstract # 44
Assessment of metabolic flexibility of aged and adult mice using three non-invasive, indirect
calorimetry-based methods.
Loes P.M. Duivenvoorde, Evert M. van Schothorst, Hans Swarts, and Jaap Keijer
Background Indirect calorimetry (InCa) is a non-invasive method that can potentially be used to
assess metabolic and age-related flexibility as a measure for metabolic health.
Objective To test three InCa-based methods to assess their use for health assessment of mice.
Methods Three InCa methods; i) diurnal pattern of respiratory exchange ratio (RER), ii) RER
response to a glucose bolus and iii) response to mild oxygen restriction (OxR, 14.5 % O 2 ), were
tested in aged (72 weeks at start) and adult (10 weeks at start) wild-type male C57Bl/6JOlaHsd
mice. Analysis was repeated to assess response stability.
Results Aged mice showed higher adiposity and lower white adipose tissue mitochondrial density,
indicative of age-impaired metabolic health. First, natural diurnal patterns of respiratory exchange
ratio were followed for 24 hours under standard conditions. These were not stable with time.
Second, fasted mice received a glucose bolus to test switch-effectiveness from fat to glucose
oxidation. No differences between adult and aged mice were seen. Third, mice were challenged
with OxR and adaptation was assessed. In contrast to adult mice, aged mice did not maintain
reduced oxygen consumption under OxR at both time periods. OxR thus appeared most sensitive to
stably detect differences between both groups. Gene expression and biochemical analyses showed
that OxR affected glucose and lactate homeostasis in liver and adipose tissue, supporting the
observed differences in oxygen consumption.
Conclusion InCa analysis of the response to OxR is a sensitive and reproducible method to noninvasively
measure age-impaired metabolic health in aged mice.