1. Investigación

The profiles of plasma leptin levels in pregnant and lactating rats and their offspring were determined. The plasma leptin levels increased on days 12 and 20 of gestation and declined on day 21 of gestation, remaining at this level during lactation. These changes were similar for lumbar adipose tissue weight, and a significant correlation was found when both variables were plotted with individual values. During the last 2 days of intrauterine life, the plasma leptin levels in the fetuses were in the same range as in their mothers, declining from day 20 to day 21. On the 1st day of life, the leptin levels increased to decline in suckling newborns after 4 days, remaining stable until day 20 of life. The enhancement in maternal white adipose tissue mass that takes place during pregnancy and its decline around parturition and lactation are proposed to contribute actively to the changes in the plasma leptin profile detected at these stages. Besides the contribution of placental leptin for the fetus and milk leptin for the suckling newborn, it is proposed that brown adipose tissue, which is the first form of adipose tissue that appears during development in the rat, is responsible for most of the changes in plasma leptin levels seen around birth, whereas its later decline could be mediated by the hormonal changes occurring after birth.

To determine the effect of under-nutrition during suckling in adults, at delivery female Sprague Dawley rats were allowed to lactate litters of either eight (controls) or sixteen pups each (large litter, LL). The amount of milk taken by LL pups was less than the controls and the concentration of triacylglycerols (TG) in the milk of the former was lower. The increase of both body weight and length in LL was lower than in the controls during suckling. At weaning, pups were allowed to eat ad libitum a standard diet and whereas at 20 months female body weight did not differ between LL and control rats, LL males weighed less than controls. Plasma NEPA were lower in male LL than in controls at 10 months, leptin at 10 and 16 months and TG and VLDL-TG at 20 months, with no differences in females. When 20 months old, lumbar and epididymal adipose tissue weights were lower in male LL than in controls, but not in females. The increase in plasma insulin after oral glucose load was lower in LL than in controls, both in males and females at 4 and 16 months, and only in males at 10 months, whereas the change in plasma glucose remained constant between the groups. Results indicate that both the pancreatic [3-cell function and insulin sensitivity and adipose tissue metabolism are independently programmed as a consequence of under-nutrition during suckling, the effect being more manifest for males than for females.

During the first two thirds of gestation, coinciding with a minimal accretion by the conceptus, the mother is in an anabolic state which is supported by her hyperphagia and the more efficient conservation of exogenous nutri~nts whenever she eats. During this phase maternal fat depots are accumulated thanks to the enhancement in adipose tissue lipogenic and glycerolgenic activity. In the latter part of gestation, on the contrary, the rapid fetal growth is sustained by the intense transfer of nutrients from maternal circulation. Glucose is quantitatively the most abundant of the different substrates that cross the placenta and despite enhanced maternal gluconeogenesis this transfer is the cause of the maternal tendency to hypoglucemia. This causes a switch to a net catabolic state which is specially evident in the net breakdown of fat depots. Enhanced release of adipose tissue lipolytiL- products, FFA and glycerol. facilitates the liver synthesis of triglycerides and their later release into circulation associated to VLDL. Glycerol is also used as an important ,, luconeogenic substrate and FFAs are hroken d~wn through 13-oxidation for ketone body synthesis. These pathwa/s become heightened when food is withheld and actively contribute to the availability of fuels to the fetus which becomes partially preserved from maternal metabolic insult. Enhanced liver production of VLDL triglycerides and decreased extrahepatic lipoprotein lipase contribute to exaggerated maternal hypertriglyceridemia which, besides being a floating metabolic reserve for emergency conditions such as starvation, constitutes an essential substrate for milk synthesis around parturition in preparation for lactation.

Pieces of lumbar adipose tissue from 19-day pregnant rats and their virgin controls were incubated in the presence of albumin, glucose, U- 14C-glycerol, and either bovine insulin (200 µU/ml) or adrenaline (2.6 µM). The rate of glycerol release in the medium was augmented in both fed and 48-hour fasted pregnant rats. Insulin reduced this parameter in tissues from pregnant rats but not from controls. Adrenaline enhanced it in all groups, especially in tissues from fed pregnant rats. The rates of CO2 , fatty acids and glyceride glycerol formation from glycerol were higher and the effect of insulin was greater in pregnant than in control rats when fed. Fasting produced a decrease in all these parameters, the effect being greater in pregnant than in control rats. The augmented sensitivity of adipose tissue from the mother allows for a rapid switch from the anabolic to the catabolic state according to the necessities of the fetus.