Calorie restricted rats do not increase metabolic rate post-LPS, but do seek out warmer ambient temperatures to behaviourally induce a fever

Abstract

Due to previous work where we have demonstrated attenuated febrile responses post-lipopolysaccharide (LPS) in calorie restricted (CR) rodents we aimed to explore metabolic rate and behavioral thermoregulation in these CR animals post-LPS. Male Sprague–Dawley rats fed ad libitum (AL) or restricted to 50% (CR50%) of the AL animals' food intake for 28days were injected on the 29th day with 50μg/kg of LPS. Core body temperature (Tb), self-selected self-selected ambient temperature (Ta), indirect calorimetry [to determine energy expenditure (EE) and respiratory quotient (RQ)] were measured in AL and CR animals for 8hours post-LPS. The CR rats chose to sit at a higher Ta (28.1±0.4°C) compared to the AL rats (23.7±1.4°C) at baseline and the AL rats chose to sit at a warmer Ta from 30min until 420min post-LPS; however, the CR rats selected a warmer Ta only at 270min post-LPS. AL rats demonstrated a higher Tb compared to baseline at 120, 150, and from 240 until 480min post-LPS. In contrast to our previous findings the CR rats also demonstrated a higher Tb compared to baseline for most of the time between 270 and 420min post-LPS. When allowed to select a warmer Ta the CR rats do so and thereby mount a febrile response, although significantly delayed and shorter-lived. In the indirect calorimetry experiment the AL rats demonstrated an elevated Tb from 150 until 480min post-LPS; however, the CR rats fever profile was attenuated, with the only increase occurring at 270min post-LPS. Indirect calorimetry indicated that the CR rats demonstrated significantly reduced EE (−17.9%±1.3) compared to the AL rats at baseline. After LPS, the AL rats demonstrated an increase in EE at multiple time points between 90 and 420min, whereas no change was observed in the CR rats. The AL and CR rats demonstrated similar profiles of RQ at baseline and after LPS the AL rats demonstrated a decrease in their RQ at 360, 450, and 480min, whereas the CR rats demonstrated no difference. The metabolic cost for rats to mount a fever during a period of low food availability may outweigh the benefits of producing a febrile response to a relatively small dose of LPS.