Limits to sustained energy intake XXIV: impact of suckling behaviour on the body temperatures of lactating female mice.

The objective of this study was to investigate the potential causes of high body temperature (Tb) during lactation in mice as a putative limit on energy intake. In particular we explored whether or not offspring contributed to heat retention in mothers while suckling. Tb and physical activity were monitored in 26 female MF1 mice using intraperitoneally implanted transmitters. In addition, maternal behaviour was scored each minute for 8 h d(-1) throughout lactation. Mothers that raised larger litters tended to have higher Tb while nursing inside nests (P < 0.05), suggesting that nursing offspring may have influenced heat retention. However, Tb during nursing was not higher than that recorded during other behaviours. In addition, the highest Tb during the observation period was not measured during nursing behaviour. Finally, there was no indication that mothers discontinued suckling because of a progressive rise in their Tb while suckling. Tb throughout lactation was correlated with daily increases in energy intake. Chronic hyperthermia during lactation was not caused by increased heat retention due to surrounding offspring. Other factors, like metabolic heat produced as a by-product of milk production or energy intake may be more important factors. Heat dissipation limits are probably not a phenomenon restricted to lactation.

Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets.

Lactation is one of the most energetically expensive behaviours, and trade-offs may exist between the energy devoted to it and somatic maintenance, including protection against oxidative damage. However, conflicting data exist for the effects of reproduction on oxidative stress. In the wild, a positive relationship is often observed, but in laboratory studies oxidative damage is often lower in lactating than in non-breeding animals. We hypothesised that this discrepancy may exist because during lactation food intake increases many-fold resulting in a large increase in the intake of dietary antioxidants which are typically high in laboratory rodent chow where they are added as a preservative. We supplied lactating and non-breeding control mice with either a standard or low antioxidant diet and studied how this affected the activity of endogenous antioxidants (catalase, superoxide dismutase; SOD, and glutathione peroxidise; GPx) and oxidative damage to proteins (protein carbonyls, PC) in liver and brain tissue. The low antioxidant diet did not significantly affect activities of antioxidant enzymes in brain or liver, and generally did not result in increased protein damage, except in livers of control mice on low antioxidant diet. Catalase activity, but not GPx or SOD, was decreased in both control and lactating mice on the low antioxidant diet. Lactating mice had significantly reduced oxidative damage to both liver and brain compared to control mice, independent of the diet they were given. In conclusion, antioxidant content of the diet did not affect oxidative stress in control or reproductive mice, and cannot explain the previously observed reduction in oxidative stress in lactating mammals studied in the laboratory. The reduced oxidative stress in the livers of lactating mice even under low antioxidant diet treatment was consistent with the 'shielding' hypothesis.

Factors influencing individual variability in high fat diet-induced weight gain in out-bred MF1 mice.

Easy access to high-energy palatable foods has been suggested to have contributed to the world-wide obesity epidemic. However, within these 'obesogenic' environments many people manage to remain lean. Mice also show variability in their weight gain responses to high-fat diet (HFD) feeding and their weight loss responses to calorically restricted (CR) feeding. In this study we investigated which factors contribute to determining susceptibility to HFD-induced obesity in mice, and whether the responses in weight gain on HFD are correlated with the responses to CR. One-hundred twenty four mice were exposed to 30% CR for 28days followed by a 14day recovery period, and subsequent exposure to 60% HFD for 28days. Responses in various metabolic factors were measured before and after each exposure (body mass; BM, body composition, food intake; FI, resting metabolic rate; RMR, physical activity, body temperature and glucose tolerance; GT). Weight changes on HFD ranged from -1 to 26%, equivalent to -0.2g to 10.5g in absolute mass. Multiple regression models showed that fat free mass (FFM) of the mice before exposure to HFD predicted 12% of the variability in weight gain on HFD (p<0.001). Also, FI during the first week of HFD feeding predicted 20% of the variability in BM and fat mass (FM) gain 4weeks later. These data may point to a role for the reward system in driving individual differences in FI and weight gain. Weight gain on the HFD was significantly negatively correlated to weight loss on CR, indicating that animals that are poor at defending against weight gain on HFD, were also poor at defending against CR-induced weight loss. Changes in FM and FFM in response to HFD or CR were not correlated however.

Limits to sustained energy intake. XX. Body temperatures and physical activity of female mice during lactation.

Lactating animals consume greater amounts of food than non-reproductive animals, but energy intake appears to be limited in late lactation. The heat dissipation limit theory suggests that the food intake of lactating mice is limited by the capacity of the mother to dissipate heat. Lactating mice should therefore have high body temperatures (Tb), and changes in energy intake during lactation should be reflected by variation in Tb. To investigate these predictions, 26 mice (Mus musculus) were monitored daily throughout lactation for food intake, body mass, litter size and litter mass. After weaning, 21 days postpartum, maternal food intake and body mass were monitored for another 10 days. Maternal activity and Tb were recorded every minute for 23 h a day using implanted transmitters (vital view). Energy intake increased to a plateau in late lactation (days 13-17). Daily gain in pup mass declined during this same period, suggesting a limit on maternal energy intake. Litter size and litter mass were positively related to maternal energy intake and body mass. Activity levels were constantly low, and mice with the largest increase in energy intake at peak lactation had the lowest activity. Tb rose sharply after parturition and the circadian rhythm became compressed within a small range. Tb during the light period increased considerably (1.1 ° C higher than in baseline), and lactating mice faced chronic hyperthermia, despite their activity levels in lactation being approximately halved. Average Tb increased in relation to energy intake as lactation progressed, but there was no relationship between litter size or litter mass and the mean Tb at peak lactation. These data are consistent with the heat dissipation limit theory, which suggests performance in late lactation is constrained by the ability to dissipate body heat.

Effects of selective breeding for increased wheel-running behavior on circadian timing of substrate oxidation and ingestive behavior.

Fluctuations in substrate preference and utilization across the circadian cycle may be influenced by the degree of physical activity and nutritional status. In the present study, we assessed these relationships in control mice and in mice from a line selectively bred for high voluntary wheel-running behavior, either when feeding a carbohydrate-rich/low-fat (LF) or a high-fat (HF) diet. Housed without wheels, selected mice, and in particular the females, exhibited higher cage activity than their non-selected controls during the dark phase and at the onset of the light phase, irrespective of diet. This was associated with increases in energy expenditure in both sexes of the selection line. In selected males, carbohydrate oxidation appeared to be increased compared to controls. In contrast, selected females had profound increases in fat oxidation above the levels in control females to cover the increased energy expenditure during the dark phase. This is remarkable in light of the finding that the selected mice, and in particular the females showed higher preference for the LF diet relative to controls. It is likely that hormonal and/or metabolic signals increase carbohydrate preference in the selected females, which may serve optimal maintenance of cellular metabolism in the presence of augmented fat oxidation.

Limits to sustained energy intake XII: is the poor relation between resting metabolic rate and reproductive performance because resting metabolism is not a repeatable trait?

Many studies have investigated the consequences of individual variation in resting metabolic rate at thermoneutrality (RMRt) on reproductive performance. Despite strong theoretical reasons for expecting such an association, results have generally been disappointing. A fundamental assumption of these studies is that RMRt is a repeatable trait. We examined repeatability of RMRt in female MF1 mice over short (15 days apart; N=238) and long intervals (110 days apart; N=33). In the long-term experiment, after the first RMRt measurement, females were separated in two groups: the first was kept virgin (N=16); the second was allowed to breed (N=17) and measured 15 days after they had weaned their pups. We also examined the association between RMRt and reproduction. We used Pearson's correlation (r) and intraclass correlation coefficients (rho) to estimate repeatability. There was a strong effect of body mass on RMRt for all measurements. Over the short interval, repeatability was significant for body mass (r=0.86; rho=0.86), RMRt (r=0.68; rho=0.68,) and residual-RMRt (r=0.58; rho=0.58). Over long intervals, repeatability of residual-RMRt was high in virgin females (r=0.59; rho=0.60), but not in the breeders (r=0.38; rho=0.39); body mass was repeatable only for non-breeders measured by r (r=0.55). There was no significant correlation between RMRt or residual-RMRt and litter size or litter mass. In conclusion, RMRt and residual-RMRt are highly repeatable traits in virgin MF1 female mice. The lack of association between non-reproductive RMRt and reproductive performance in MF1 mice does not come about because of its poor repeatability.

Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity.

OBJECTIVE: Increased dietary fat intake is a precipitating factor for the development of obesity and associated metabolic disturbances. Physically active individuals generally have a reduced risk of developing these unhealthy states, but the underlying mechanisms are poorly understood. In the present study, we investigated the effects of feeding a high-fat diet (HFD) on obesity development and fuel homeostasis in male and female mice with a trait for increased physical activity and in their controls. METHODS: Male and female mice selectively bred for a high level of wheel running behavior over 30 generations and nonselected controls (background strain Hsd:ICR) were maintained on a standard lab chow high-carbohydrate diet (HCD) or on an HFD (60% fat). Food intake, body weight, indirect calorimetry parameters, spontaneous locomotor activity and several hormones relevant to metabolism and energy balance were measured. RESULTS: On HFD, mice reduced food intake and increased body fat mass and plasma leptin levels, with the notable exception of the selected females, which increased their ingested calories without any effects on body mass or plasma leptin levels. In addition, they had an elevated daily energy expenditure (DEE), increased spontaneous cage activity ( approximately 700% relative to controls) and higher resting metabolic rate (RMR) on the HFD compared with feeding the HCD. The selected males also had a higher DEE compared with controls, but no interaction with diet was observed. On HCD, adiponectin levels were higher in selected male, but not female, mice relative to controls. A marked increase in the level of plasma adiponectin was observed on the HFD in selected females, an effect of diet that was not observed in selected males. CONCLUSION: Genetically based high locomotor activity renders female, but not male, mice resistant to HFD-induced obesity by alterations in behavioral, endocrine and metabolic traits that facilitate fat utilization rather than limiting HFD intake.

Plasma adiponectin is increased in mice selectively bred for high wheel-running activity, but not by wheel running per sé.

Mice selectively bred for high wheel-running activity (S) have decreased fat content compared to mice from randomly bred control (C) lines. We explored whether this difference was associated with alterations in levels of circulating hormones involved in regulation of food intake and energy balance, and whether alterations were caused by the presence of a running wheel. Plasma levels of leptin, adiponectin, and corticosterone as well as body composition were analyzed in male S mice housed with (+) and without (-) access to running wheels at ages of 10 and 18 months. These levels were compared to those found in C+ mice. Plasma corticosterone did not differ among groups. While plasma leptin levels tended to be lower in S+ mice as compared to S- or C+ mice, these differences were largely attributable to differences in fat content. Adiponectin levels were increased in S mice (+60%) compared to C mice, irrespective of wheel access. High levels of this hormone may be a trait co-segregated in mice bred for high wheel-running activity.