The source of leptin, but not leptin depletion in response to food restriction, changes during early pregnancy in mice

Maternal food restriction during pregnancy results in adverse consequences for offspring, including obesity and cardiovascular disease. Early pregnancy is a critical period for this programming effect. Leptin is a regulator of energy homeostasis that also affects placental and fetal development. As food restriction results in decreased serum leptin levels, at least in non-pregnant animals, leptin depletion may be one mechanism by which food restriction affects development. The objective of this study was to test whether moderate food restriction affects serum leptin concentrations during the first half of pregnancy. We found that restriction to 50% of ad libitum consumption levels resulted in a significant decrease in serum leptin concentrations in both pregnant and nonpregnant female mice. There was no significant difference in serum leptin concentrations between non-pregnant females and at pregnancy day 11.5 when fed ad libitum. However, there was a difference in the source of leptin during pregnancy, with greater production in visceral fat in pregnant mice, and greater production in subcutaneous fat in non-pregnant mice. Leptin concentrations were dependent on time of day and time of sampling relative to feeding, particularly in restricted mice. There was a significant difference in serum leptin concentrations between fed and restricted mice when they were fed and sampled in afternoon, but not when they were fed and sampled in morning. We conclude that food restriction results in a significant decrease in leptin concentration during the first half of pregnancy in mice, but that detection of this relationship is subject to experimental design considerations.