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.

Para estudiar las variaciones de la funci6n tiroidea en ratas diabeticas, ratas mantenidas con una dieta pobre en yodo se inyectaron con estreptozotocin y fueron comparadas con controles inyectadas con el medic y alimentadas con la misma dieta. Las ratas tratadas con estreptozotocin mostraron una intensa diuresis e hiperglucemia durante los 29 dias despues del tratamiento. Estes animales presentaban una concentraci6n normal de 127PBI plasmatico, pero una captaci6n tiroidea de 13'1 y una concentraci6n de 131PBI plasmatico, reducidas a las 24 horas de la inyecci6n del trazador. Los animales tratados con estreptozotocin mostraron un elevado contenido en 1271 en sus tiroides y una alterada distribuci6n porcentual de iodoaminoacidos en la glandula, con una aumentada proporci6n de DIT y una disminuida proporci6n de r. y T,. Los resultados permiten sugerirque la sintesis y secreci6n de las hormonas tiroideas se encuentran reducidas en los animales diabeticos. Esta disminuida tunci6n tiroidea concuerda con la disminuida efectividad hormonal del TSH descrita por otros autores

It has been proposed that the lipolytic effect of serum is based on the presence of either lipoproteins or catecholamines. To test these hypotheses, pieces of epididymal fat pads from fed rats were incubated in the presence of albumin and glucose for 120 min. The addition of rat serum (5 µ.I/vial) enhanced the rates of both glycerol release to the media and [U-14C] glycerol utilization by the tissue. Heparin did not alter these parameters or the response produced by serum. VLDL from rat plasma also enhanced glycerol release and utilization for the formation of CO2 and lipids, and heparin significantly augmented these effects. Neither of the conditions studied affected the percentual distribution of 14C-lipid fractions in the tissues. It is known that in similar conditions to those used in the present study, adrenaline produces a decrease in the utilization of glycerol. Thus our findings do not support the proposed hypothesis explaining the fat-mobilizing action of serum, the mechanism of which remains to be determined.

[U-14C] glucose utilization by pieces of epididymal fat-pad was studied in streptozotocin-diabetic rats, food-restricted animals, and normal controls. Both CO2 and fatty acids formation were greatly reduced in tissues from the diabetic animals treated or not with insulin and this change was milder in tissues from foodrestricted rats. A positive correlation was found between [' 4C] glucose utilization in vitro and plc:J.sma RIA-insulin levels when values from all animals were pooled. The percentual response to high doses of insulin was small in adipose tissue from streptozotocin-diabetic animals for CO2 and total lipids formation, but it was high for fatty acids synthesis; the response in food-restricted animals was high and was greatly augmented in tissues from the streptozotocin-diabetic rats treated with insulin. Results indicate that in adipose tissue from streptozotocin-diabetic animals the alteration of insulin responsiveness occurs distal to the receptor events and that impaired basal glucose metabolism is a direct consequence of their hypoinsulinemia.

To determine whether the reduced lipoprotein lipase activity in adipose tissue in late pregnancy corresponds to parallel changes in the uptake of triglyceride fatty acids, isolated adipocytes from 19- and 21-day pregnant rats and virgin controls were incubated for different periods in the presence of rat plasma triglyceride-rich lipoproteins with their esterified fatty acids of neutral glycerides (triglycerides) labelled with 3H. The hydrolysis of triglycerides and uptake of fatty acids by the adipocytes increased linearly and parabolically with respect to the incubation time and were always lower in cells from pregnant animals than from controls. Addition of heparin to the incubation medium produced similar increases in hydrolysis and uptake in all groups. Results indicate that the diminished uptake of triglyceride fatty acids by adipose tissue contributes to hypertriglyceridemia in late pregnancy which is counteracted by lipogenesis increase tc maintain the mother's augmented body fat.

La principal fuente de vitamina A o retino/ del organismo son los B-carotenos de las plantas. En las células de la mucosa intestinal son escindidos a retina/, que es reducido a retino/. En su mayor parte, en la propia mucosa el retino/ es esterificado con palmitoil-CoA por acción de la acil-CoA: retino/ aci/- transferasa (ARAT), y los esteres de retino/ salen a la circulación unidos a los quilomicrones, a los que acompañan en su metabolismo hasta el hígado. En este órgano son captados por sus células parenquimatosas, pero se acumulan preferentemente en las células estelares, y en el proceso tiene lugar la hidrólisis y reesterificación de dichos esteres de retino/, con participación de proteínas intracelulares específicas que enlazan retino/ (CRBP) o ácido retinoico (CRABP). La secreción hepática se realiza en forma de retino/ asociado a una proteína plasmática que lo enlaza de forma específica (RBP), que es sintetizada en el propio hígado, y que en sangre se une a la pre-albúmina (transtiretina o TTR), la cual enlaza a su vez hormonas tiroideas. En los tejidos extrahepáticos hay también síntesis de RBP y de TTR; también a receptores que reconocen y unen a la RBP plasmática, y por este proceso el retino/ es captado, mientras que la RBP queda libre en plasma para su posterior eliminación por vía renal. Cuando se estudia en sujetos sanos en ayunas, la vitamina A no aparece asociada en plasma a ninguna de las lipoproteínas circulantes. A pesar de ello, se observa una correlación positiva, significativa y lineal entre los niveles de vitamina A y los de triglicéridos y colesterol. También se observa una correlación significativa y lineal entre los niveles de vitamina A y los de triglicéridos y colesterol. También se observa una correlación significativa y lineal entre los niveles plasmáticos de vitamina A y los de triglicéridos de VLDL y los de coles tero/ de LDL. Sobre la base de estos resultados y que ambas lípoproteínas llevan la apoproteína 8-100, de origen hepático, como también lo es la RBP, se propone que estas correlaciones son indirectas y relacionadas con la actividad secretora de proteínas del hígado. Esta hipótesis coincide también con la correlación encontrada por otros autores entre los niveles de éstas y otras proteínas plasmáticas de origen hepático en situaciones patológicas.

A technique previously used to study placental transfer in pregnant rats, consisting of labeled tracer infusion through the left uterine artery, was employed to determine the utilization oflipogenic substrates by periuterine adipose tissue in the fed and 48-hr starved female virgin rat. After 20 min infusion with either D[U- 14C]glucose, L-[U- 14C]alanine, [U14C]glycerol or L-[U- 14C]lactate, the radioactivity appearing in periuterine adipose tissue 14C-labeled lipids from the left side was always higher than that appearing in tissue from the right side. Negligible radioactivity was detected in the tissue from either side when the infusion was done with non-metabolizable derivatives such as L-[1- 14C]glucose or [1- 14C]a-aminoisobutyric acid. Simultaneous infusion ofL-[U- 14C]alanine and an alanine transaminase inhibitor (aminooxyacetic acid) into the left uterine artery completely blocked the conversion of the alanine into periuterine adipose tissue 14C-labeled lipids. The utilization of the infused substrate for fatty acids and glyceride-glycerol synthesis by the tissue was quantified by taking into account the infused radioactivity, the difference in the amount of 14C-labeled lipids appearing in periuterine adipose tissue on the left and the right sides, the arterial plasma concentration of the studied metabolite, and the uterine horn blood flow. In fed animals, the highest fatty acid synthesis was found with lactate, followed by glucose, alanine, and glycerol. This process was intensely decreased with all the substrates in 48-hr starved rats. In fed animals the synthesis of glyceride-glycerol was highest with glucose followed by lactate, alanine, and glycerol. In the starved rats it did not change with lactate and decreased with both alanine and glycerol. Besides validation of the technique for the study of periuterine adipose tissue metabolism in situ, results show the efficient utilization of lactate as lipogenic and of glucose as glycerogenic substrates. On the basis of the known capacity of adipose tissue to synthesize alanine from other amino acids, we propose that in the fed state this tissue may use different amino acids for lipogenesis. The negligible use of glycerol by periuterine adipose tissue in situ contrasts to its known utilization in vitro indicating that, whereas glycerokinase activity in the tissue may have a role in the re-utilization of glycerol released into the tissue, it does not contribute to the use of circulating glycerol.