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.

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.

Human very-low-density lipoproteins (VLDL) were subfractionated by heparin-Sepharose chromatography into an unbound (:\I and three bound (B, C and D) populations at increasing ionic strengths. Subfractions were characterized regarding their chemic;,[ composition and efficiency of triacylglycerol hydrolysis by rat adipose tissue LPL. The triacylglycerol content decreased, whcrca, the cholesterol and protein contents increased from subfractions A and B to subfraction D. VLDL-D showed the highest ap<' E/apo C ratio, though all the subfractions contained appreciable apo E. Appearance of VLDL-A resulted from exceeding the binding capacity of the column, since practically all its particles eluted at positions of bound VLDL under re-chromatograph~ Subfractions B, C and D stimulated LPL activity on emulsified tri[ 14C]oleoylglycerol to a similar extent, indicating that their 3P'' C-11 content was equally effective activating LPL. Incubation of tri[ 14C]oleoylglycerol labeled VLDL subfractions with fat pad pieces in the presence or absence of heparin resulted in greater hydrolysis and fatty acid uptake for VLDL-B and -C than f.•1 VLDL-D, a pattern observed over a wide range of LPL activities in the media. We conclude: (1) any VLDL particle can intcr;t,1 with heparin, which is consistent with the presence of apo E in all the subfractions, and (2) triacylglycerols in apo E-rich VLDI are less efficiently hydrolyzed by LPL than those in apo E-poor particles. We propose that richness in apo E impairs LPL acu"r upon VLDL and decreases the rate of delivery of fatty acids to peripheral tissues.