Effect of Food Restriction of Plasma Leptin Concentrations in Pregnant and Nonpregnant Female Mice.

Abstract

Our long term goal is to test whether leptin depletion is responsible for some of the effects of maternal nutrient restriction during early pregnancy on the placenta and embryo. To test this hypothesis, it is first necessary to establish whether plasma leptin concentrations decrease in response to food restriction in pregnant female mice. Leptin, a peptide hormone produced by adipose tissue, has been found to correlate to body mass index or other measures of adiposity in multiple species. Leptin release is also known to be regulated by circadian rhythm, food intake, insulin, and corticosteroids. Accordingly, leptin levels fall even more rapidly following food restriction than would be explained by fat loss alone. However, there is reason to doubt that this is the case in female mice, particularly during pregnancy. During later pregnancy, leptin concentrations increase independently of adiposity, a process that begins around day 11 in mice. A previous study found that leptin actually increases in response to food restriction during the latter half of pregnancy in rats. Another found that restriction to 60% of ad libitum consumption led to significantly decreased plasma leptin concentrations in male, but not female mice. The goal of this study was to determine whether 50% food restriction affects plasma leptin concentrations in pregnant and non-pregnant female mice. Thirty-six female mice were fed ad libitum (ad lib) or fed 50% of the food consumed by ad lib-fed mice (restricted) at 1600h each day for 10 days. On the tenth day, terminal blood samples were taken from three animals on each diet every four hours. Leptin concentrations differed most between diet groups in the afternoon and evening, but were not different in the morning. We then compared plasma leptin concentrations in samples taken at 1600h after 10 days in each treatment group: non-pregnant, ad lib fed (n=8), non-pregnant, restricted (n=8), pregnant (d11.5) ad lib (n=7) and pregnant restricted (n=4). Two additional plug-positive mice on the restricted diet did not maintain pregnancy, and were excluded from analysis. Initial mouse weights were the same across treatment groups. Final weights were significantly higher in pregnant vs non-pregnant animals fed ad lib, but similar in pregnant and non-pregnant animals on the restricted diet. Mouse weights on the restricted diet were significantly lower than those of ad lib fed mice. Leptin concentrations were similar in pregnant and non-pregnant mice fed ad lib. Leptin was significantly lower in both pregnant and non-pregnant mice following food restriction (p<0.0001), but fell more dramatically in the pregnant animals. Preliminary results indicated that when both groups of pregnant mice were fed in the morning, and blood samples were collected in the morning, leptin concentrations were higher in the restricted group, perhaps due to observed differences in the timing of food consumption. We conclude that plasma leptin concentration does fall in response to food restriction in pregnant and non-pregnant female mice, but the timing of sampling and feeding are critical. This work is supported by NIH HD055231 (poster)