Limits to sustained energy intake. XXII. Reproductive performance of two selected mouse lines with different thermal conductance.

Maximal sustained energy intake (SusEI) appears limited, but the factors imposing the limit are disputed. We studied reproductive performance in two lines of mice selected for high and low food intake (MH and ML, respectively), and known to have large differences in thermal conductance (29% higher in the MH line at 21°C). When these mice raised their natural litters, their metabolisable energy intake significantly increased over the first 13 days of lactation and then reached a plateau. At peak lactation, MH mice assimilated on average 45.3% more energy than ML mice (222.9±7.1 and 153.4±12.5 kJ day(-1), N=49 and 24, respectively). Moreover, MH mice exported on average 62.3 kJ day(-1) more energy as milk than ML mice (118.9±5.3 and 56.6±5.4 kJ day(-1), N=subset of 32 and 21, respectively). The elevated milk production of MH mice enabled them to wean litters (65.2±2.1 g) that were on average 50.2% heavier than litters produced by ML mothers (43.4±3.0 g), and pups that were on average 27.2% heavier (9.9±0.2 and 7.8±0.2 g, respectively). Lactating mice in both lines had significantly longer and heavier guts compared with non-reproductive mice. However, inconsistent with the 'central limit hypothesis', the ML mice had significantly longer and heavier intestines than MH mice. An experiment where the mice raised litters of the opposing line demonstrated that lactation performance was not limited by the growth capacity of offspring. Our findings are consistent with the idea that the SusEI at peak lactation is constrained by the capacity of the mothers to dissipate body heat.

Limits to sustained energy intake. XV. Effects of wheel running on the energy budget during lactation.

The capacity of animals to dissipate heat may constrain sustained energy intake during lactation. We examined these constraints at peak lactation in MF1 mice that had ad libitum access to food, or that had to run a pre-set target on running wheels to obtain ad libitum access to food. The voluntary distance run decreased sharply during pregnancy and peak lactation. When lactating females were provided with 80% of their estimated food requirements, and had to run pre-set distances of 2, 4 or 6 km before given access to additional ad libitum food, most of them did not complete the running target during late lactation and the mice with the highest targets failed to reach their targets earlier in lactation. There were consequently significant group differences in asymptotic food intake (2 km, 16.97 ± 0.40 g day(-1); 4 km, 14.29 ± 0.72 g day(-1); and 6 km, 12.65 ± 0.45 g day(-1)) and weaned litter masses (2 km, 71.11 ± 2.39 g; 4 km, 54.63 ± 4.28 g and 6 km, 47.18 ± 2.46 g). When the females did run sufficiently to gain ad libitum food access, their intake did not differ between the different distance groups or from controls that were not required to run. Thus, despite being physically capable of running the distances, mice could not exercise sufficiently in lactation to gain regular ad libitum access to food, probably because of the risks of hyperthermia when combining heat production from exercise with thermogenesis from lactation.

Limits to sustained energy intake. XVI. Body temperature and physical activity of female mice during pregnancy.

Lactation is the most energy-demanding phase of mammalian reproduction, and lactation performance may be affected by events during pregnancy. For example, food intake may be limited in late pregnancy by competition for space in the abdomen between the alimentary tract and fetuses. Hence, females may need to compensate their energy budgets during pregnancy by reducing activity and lowering body temperature. We explored the relationships between energy intake, body mass, body temperature and physical activity throughout pregnancy in the MF1 mouse. Food intake and body mass of 26 females were recorded daily throughout pregnancy. Body temperature and physical activity were monitored every minute for 23 h a day by implanted transmitters. Body temperature and physical activity declined as pregnancy advanced, while energy intake and body mass increased. Compared with a pre-mating baseline period, mice increased energy intake by 56% in late pregnancy. Although body temperature declined as pregnancy progressed, this served mostly to reverse an increase between baseline and early pregnancy. Reduced physical activity may compensate the energy budget of pregnant mice but body temperature changes do not. Over the last 3 days of pregnancy, food intake declined. Individual variation in energy intake in the last phase of pregnancy was positively related to litter size at birth. As there was no association between the increase in body mass and the decline in intake, we suggest the decline was not caused by competition for abdominal space. These data suggest overall reproductive performance is probably not constrained by events during pregnancy.

Effects of chronic oral rimonabant administration on energy budgets of diet-induced obese C57BL/6 mice.

The endocannabinoids have been recognized as an important system involved in the regulation of energy balance. Rimonabant (SR141716), a selective inverse agonist of cannabinoid receptor 1 (CB1), has been shown to cause weight loss. However, its suppressive impact on food intake is transient, indicating a likely additional effect on energy expenditure. To examine the effects of rimonabant on components of energy balance, we administered rimonabant or its vehicle to diet-induced obese (DIO) C57BL/6 mice once daily for 30 days, by oral gavage. Rimonabant induced a persistent weight reduction and a significant decrease in body fatness across all depots. In addition to transiently reduced food intake, rimonabant-treated mice exhibited decreased apparent energy absorption efficiency (AEAE), reduced metabolizable energy intake (MEI), and increased daily energy expenditure (DEE) on days 4-6 of treatment. However, these effects on the energy budget had disappeared by days 22-24 of treatment. No chronic group differences in resting metabolic rate (RMR) or respiratory quotient (RQ) (P > 0.05) were detected. Rimonabant treatment significantly increased daily physical activity (PA) levels both acutely and chronically. The increase in PA was attributed to elevated activity during the light phase but not during the dark phase. Taken together, these data suggested that rimonabant caused a negative energy balance by acting on both energy intake and expenditure. In the short term, the effect included both reduced intake and elevated PA but the chronic effect was only on increased PA expenditure.