1. Investigación

Postnatal development of the glucose and insulin balance in offspring of ethanol-treated and control rats has been studied. Newborn rats were separated from their mothers and placed with normal lactating, nonethanol-treated dams. Prenatal exposure to ethanol led to hypoglycemia on the first day of extrauterine life and a general tendency to hyperinsulinemia during the entire postnatal period studied. The glucose-tolerance test in weaned rats (30 days old) gave a greater and faster increase than controls in levels of both glucose and plasma insulin. At adult age (90 days) the response of blood glucose to an oral glucose load in offspring from ethanol-treated mothers was not different from that in offspring from controls, but the insulin response was higher. This abnormal insulin response, such a long time after the end of ethanol exposure, suggests either a permanent alteration in the pancreatic response, or a peripheral insulin resistance and/or differences in the rate of insulin degradation in these animals.

To determine adipose tissue cellularity in hypo- and hyperthyroidism, male rats were thyroidectomized after weaning (T) and injected daily with either 0, 0.1, 1. 8, or 25 µg of L-thyroxine/100 g body weight for 40 days. They were compared with intact controls (C). Both epididymal fat-pad weight and adipocyte diameter were reduced in T+0, T+0.1 and T+25 animals. When corrected per unit of body weight, the diameters of adipocytes from T+0 and T+0. l animals were larger than in the other groups. Those same animals have reduced absolute adipocyte number but not when corrected per unit of body weight. The fat-pad protein concentration varied conversely with the fat cell diameter. These findings indicate that thyroid hormone deficiency reduces thf proliferation of fat cells in parallel with body growth while hyperthyroidism causes reduction in the size, but not the number, of fat cells which corresponds to its depletion of fat storage.

Triglyceride-rich rat lipoproteins (mainly VLDL), purified by ultracentrifugation and dialysis, were incubated for 120 min in the presence of epididymal fat-pad pieces from fed rats in media containing heparin. During this process, the lipoproteins were depleted of triglycerides and proportionally enriched with proteins, causing their increased density. After incubation, electron microscopic study of the triglyceride- rich lipoproteins revealed partially degraded structures, and some particles had atypical discoid flattened form and marked lamellar structure. These findings are in agreement with those of BLANCHETTE-MACKIE & Scow (l 976) in triglyceride hydrolysed chylomicrons and confirm their observation of monolayers formed by accumulated lipolytic products that move by lateral diffusion, giving rise to a spiral fold between the core triglycerides and the aqueous space.

Mammary gland and adipose tissue lipoprotein lipase activities have been implicated in the changes of circulating triacylglycerol levels which occur in the mother at late gestation. In the newborn the temporal accumulation of triacylglycerols in the liver coincides with the appearance of a lipoprotein lipase peak. The relationships of these changes with the rise in circulating prolactin in the mother before parturition and the extrauterine nutritional status in the offspring were studied in a postmaturity model produced in the rat by subcutaneous injection of 7 mg progesterone/ day to pregnant animals from the 20th day of gestation. Pregnant controls received the medium. Parturition occurred at day 21.5 of gestation in pregnant controls while it did not occur before the 23rd day in those receiving progesterone. At the 20th day of gestation. plasma triacylglycerol concentrations and all lipoprotein fractions (especially VLDL) were much higher in mothers not receiving progesterone than in age-matched virgins. and these differences disappeared at the 21st day of gestation. Lipoprotein lipase activity was maintained low in control mothers' adipose tissue until the 23rd postfecundation day while it greatly increased in mammary gland from parturition time. In progesterone treated mothers, both triacylglycerol and lipoprotein fractions (especially VLDL) in plasma were maintained elevated until the 23rd postfecundation day and adipose tissue and mammary gland lipoprotein lipase activities were maintained low until this time. Circulating prolactin levels increased around parturition in control mothers while they did not change in the progesterone treated mothers at any of the times studied. In offspring from control mothers. plasma triacylglycerols were low and their most abundant circulating lipoprotein fraction appeared to be LDL. In contrast to mother's liver, in offspring liver a marked lipase activity with all the inhibitory char&cteristics of lipoprotein lipase in the presence of both NaCl and protamine sulfate appeared around birth. coinciding with a sharp increase in liver triacylglycerol concentration and plasma ketone body levels. In postmature fetuses. liver lipoprotein lipase activity and triacylglycerol content decreased from the 20th to the 23rd postfecundation day while levels of both acetoacetate and beta-hydroxybutyrate rose in blood. Results indicate that increased mammary gland lipoprotein lipase in the mother may play a role in the decline of hypertriglycerolemia before parturition and that the initial change is driven by the rise in circulating prolactin at that time. On the contrary, the reduction in adipose tissue lipoprotein lipase activity in late gestation is not associated with the increase in circulating prolactin levels. We sp~cuiat.e that in offspring from control mothers. the high fat content of the mother's milk produces a substrate induction mechanisrn on Hver lipoprotein lipase converting the liver of the newiJcrn into a temporary lipid storage organ. Consumption of endogenous resources and maintenance of maternal ketone bodies transfer throl!gh the placenta ensure development of postmature fetus.

Ethanol is absorbed by diffusion across the gastric and intestinal mucosa.Following absorption, ethanol is mainly metabolized in the liver where cytosolic alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase are the principal enzymes of ethanol oxidation. Hepatic metabolism of ethanol leads to an increased formation of NADH and acetaldehyde which are the factors directly responsible for most of the metabolic disturbances produced by ethanol. Almost all lipid metabolism pathways are affected by ethanol, and hyperlipemia and fat accumulation in the liver are the most common disturbances. Several mechanisms contribute to these conditions but the ethanol effects of enhancing the arrival of lipids to the liver and decreasing their further disposition seem to be the most important. Ethanol effects on carbohydrate metabolism are also very diverse, producing either hyperglycemia or hypoglycemia depending on the availability of glycogen stores. Ethanol decreases liver gluconeogenetic activity by siphoning substrates which are converted to their reduced form. Alcohol ingestion during pregnancy may produce the fetal alcohol syndrome which causes retarded growth and abnormalities in fetal development. Animal models for this syndrome have been developed using different species. In the rat, 25% ethanol in the drinking water during pregnancy provides a daily total caloric intake similar to that of pregnant controls but causes weight reduction in both mother and fetus. Blood glucose levels are preserved in the alcoholic rat mother but liver glycogen is decreased and blood ketone bodies are augmented and these parameters are significantly affected in the fetus.

Se estudiaron el peso y longitud corporal y el contenido hipofisario de hormone del crecimiento {GH) y prolactina {PRU en a) ratas normales {N) alimentadas con purina; b) ratas tiroidectomizadas a las que se inyectaron diariamente 0 {T+0l, 0,1 (T+0,1), 1,8 {T + 1,8) o 25 {T + 25) µg de Ltiroxina/ 100 g de peso y sometidas a una dieta pobre en yodo (tipo Remington), y c) en ratas controles {C) intactas alimentadas con la misma dieta, pero con un suplemento de KIO;i suficiente para proporcionar una concentraci6n plasmatica normal de PBI. En los animates N la longitud corporal y el peso hipofisario correlacionaron con el peso corporal por regresiones de segundo orden, mientras que el contenido hipofisario de GH y PRL mostr6 un cambio de tipo lineal en relaci6n al peso corporal. La tasa de crecimiento en los animates C fue mas reducida queen los animates N. apareciendo mas disminuida todavia en las ratas T + 0. Los animates T + 0, 1 mostraron una ligera recuperaci6n de la tasa de crecimiento, mientras que en los T + 1,8 fue la misma queen las ratas C. Los animales T + 25 mostraron un peso inferior al de los animales C, a pesar de no haber observado diferencias en el tamailo corporal. En todas las series de animates, con edades superponibtes y bajo las diferentes situaciones tiroideas, el contenido hipofisario de GH y PRL no mostr6 correlaci6n de tipo lineal con la longitud corporal. Los resultados obtenidos indican que la dieta tipo Remington debe utilizarse en los estudios metabolicos con especial precauci6n y adem6s ponen de relieve la diferente sensibilidad de las hormonas tiroideas sobre el contenido hipof15ario de GH y PRL. Muestran tambien que para obtener una tasa normal de crecimiento es necesaria la presencia de un balance normal de otras funciones endocrinas.

1) Thyoridectomized rats were fed with a low iodine diet, injected daily with 0, 0.1, 1.8 or 25 µg of L-thyroxine/100 g body wt., and compared with intact controls. 2) Plasma protein-bound iodine was decreased in the rats given the 0 and 0.1 µg doses, unchanged in those given the 1.8 µg doses, unchanged in those given the 1.8 µg dose increased in those given the 25 µg one. 3) The liver content of DNA-P, phospholipid-P, proteins and fatty acids was decreased in the rats that did not receive thyr.oxine, practically recuperated in those receiving 0.1 µg and normal in those given 1.8 or 25 µg of thyroxine. 4) 3 h of starvation produced a reduction in the liver content of total fatty acids that disappeared after 24 h. 5) When fod, liver glycogen concentration was low in the rats given 25 µg of thyroxine. 6) With starvation, the fall in liver glycogen and blood glucose, and the rise in liver acetylCoA and citrate and blood glycerol concentrations were faster in the thyroidectomized rats that did not receive thyroxine than in the other groups. 7) The rise in plasma free fatty acid and blood ketone bodies concentrations were similar in all the groups, the greater level of the first parameter being observed after 6 h of starvation in the rats given 25 µg of thyroxine and in the second one after 24 h in the rats given either 0.1, 1.8 or 25 µg of thyroxine. 8) The rapid decrease in the availability of carbohydrate stores with starvation in the thyroidcctomized rats could be responsible for their fast call for lipid utilization. The slower response to fasting in the hyperthyroid animals is probably a consequence of their reduced amount of endogenous substrates to be mobilized.