Rosemary S. E. Brown

Extensive research is undertaken in rodents to determine the mechanism underlying obesity‐induced leptin resistance. While body weight is generally tightly controlled in these studies, the effect of age of experimental animals has received less attention. Specifically, there has been little investigation into leptin regulation of food intake in middle‐aged animals, which is a period of particular relevance for weight gain in humans. We investigated whether the satiety effects of leptin remained constant in young (3 months), middle‐aged (12 months) or aged (18–22 months) male mice. Although mean body weight increased with age, leptin concentrations did not significantly increase in male mice beyond 12 months of age. Exogenous leptin administration led to a significant reduction in food intake in young mice but had no effect on food intake in middle‐aged male mice. This loss of the satiety effect of leptin appeared to be transient, with leptin administration leading to the greatest inhibition of food intake in the aged male mice. Subsequently, we investigated whether these differences were due to changes in leptin transport into the brain with ageing. No change in leptin clearance from the blood or transport into the brain was observed, suggesting the emergence of central resistance to leptin in middle age. These studies demonstrate the presence of dynamic and age‐specific changes in the satiety effects of leptin in male mice and highlight the requirement for age to be carefully considered when undertaking metabolic studies in rodents.

Obesity during pregnancy represents a significant health issue and can lead to increased complications during pregnancy and impairments with breastfeeding, along with long‐term negative health consequences for both mother and offspring. In rodent models, diet‐induced obesity (DIO) during pregnancy leads to poor outcomes for offspring. Using a DIO mouse model, consisting of feeding mice a high fat diet for 8 weeks before mating, we recapitulate the effect of high pup mortality within the first 3 days postpartum. To examine the activity of the dam around the time of birth, late pregnant control and DIO dams were recorded in their home cages and the behaviour of the dam immediately before and after birth was analysed. Prior to giving birth, DIO dams spent less time engaging in nesting behaviour, while after birth, DIO dams spent less time in the nest with their pups compared to control dams, indicating reduced pup‐engagement in the early postpartum period. We have previously reported that lactogenic hormone action, mediated by the prolactin receptor, in the medial preoptic area of the hypothalamus (MPOA) is critical for the onset of normal postpartum maternal behaviour. We hypothesized that DIO dams may have lower lactogenic hormone activity during late pregnancy, which would contribute to impaired onset of normal postpartum maternal behaviour. Day 16 lactogenic activity, transport of prolactin into the brain, and plasma prolactin concentrations around birth were all similar in control and DIO dams. Moreover, endogenous pSTAT5, a marker of prolactin receptor activity, in the MPOA was unaffected by DIO. Overall, these data indicate that lactogenic activity in late pregnancy of DIO dams is not different to controls and is unlikely to play a major role in impaired onset of normal postpartum maternal behaviour.