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Biomedical subjects

E Herrera

Publications and source records attributed to E Herrera.

At least 19 recordsLinked to original sources
PubMed1996

Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids.

Liver disease is accompanied by major qualitative and quantitative disturbances in plasma lipoprotein metabolism, the extent and intensity of which depend on the degree of parenchymal damage, cholestasis, or both. The main objective of this study was to determine the cholesteryl ester transfer CETP activity and its association with the lipoprotein neutral lipid composition in patients with either liver cirrhosis or cholestasis, as compared to normal controls. Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins were measured by conventional methods, and the fatty acid composition was established by gas chromatography; CETP activity in lipoprotein-deficient plasma was measured by determining the transfer of [3H]cholesteryl esters from HDL to VLDL. Lipoprotein lipase and hepatic lipase activities were measured in post-heparin plasma by radiochemical methods. In patients with liver cirrhosis, low levels of VLDL, HDL, apo B, and Lp(a) were observed, as well as a change in the composition of HDL particles, with increases in the relative proportion of triglyceride and free cholesterol. Respectively, the last two changes could be attributed in part to the low hepatic lipase activity observed in this study, and to the low lecithin:cholesterol acyltransferase activity previously observed by others. In patients with cholestasis, a moderate hyperlipidemia due to the elevation of LDL was found. In contrast, HDL and apo A-I levels were very low reflecting a low number of HDL particles, which also had altered compositions with increases in the triglyceride and free cholesterol contents relative to apo A-I and esterified cholesterol, respectively. As regards the fatty acid composition of lipoprotein lipids, the two groups of patients showed, in general, a lower proportion of linoleic acid and a compensating higher proportion of oleic acid as compared to the controls, changes that were observed in both cholesteryl esters and triglycerides. In contrast, the proportions of oleic and palmitoleic acids in phospholipids were increased, whereas that of stearic acid was decreased in patients as compared to controls. In patients with liver cirrhosis, as well as in controls, no changes were observed in the fatty acid compositions of cholesteryl ester, triglycerides, or phospholipids among the different lipoproteins, which probably reflects the equilibration reached by the action of CETP. In patients with cholestasis, no differences were observed in fatty acid composition among the lipoprotein phospholipids but, interestingly, cholesteryl esters from VLDL had a significantly lower linoleic acid content than those from HDL, whereas triglycerides from VLDL had significantly higher oleic acid and lower linoleic acid contents than those from HDL. This distinct fatty acid composition of the neutral lipids between lipoproteins was associated with a significant decrease (25%) in the cholesteryl ester transfer activity in patients with cholestasis. We suggest that fat malabsorption due to the biliary defect may induce a decrease in cholesteryl ester transfer protein synthesis or section, which in turn would slow the equilibration of the neutral lipids among plasma lipoproteins.

Adult↗
PubMed1996

Teratogenic effects of diabetes mellitus in the rat. Prevention by vitamin E.

We wanted to determine whether administration of vitamin E could reduce the production of free radicals which could play a role in the teratogenic effects of diabetes mellitus. Diabetes was induced in Wistar rats by the intravenous administration of streptozotocin. The animals were divided into six groups: one with no supplement (D) and two, supplemented during pregnancy either with oral vitamin E (150 mg/day) (D + E) or with a placebo (safflower oil) (D + O). Three other groups were kept under the same conditions, but were treated with insulin: D + I, D + I + E and D + I + O. There were three groups of matched controls: C, C + E and C + O. All animals were killed on day 11.5 of pregnancy. In C animals the percentages of reabsorptions and malformations were 1.3 and 2%, respectively, compared with 23.6, 24.3, 6.2 and 13.2%, respectively in D and D + I groups. The crown-rump length, number of somites, and protein and DNA content were higher in C animals than in the diabetic rats, independent of insulin treatment. When vitamin E was administered no changes in these parameters were observed in C and D + I animals; however, in the D mothers it reduced the rate of embryo malformations to 4.6% and increased the crown-rump length and the number of somites. However, vitamin E did not modify the protein and DNA content and the percentage of reabsorptions. In conclusion, administration of vitamin E to diabetic animals decreases the rate of embryo malformations and increases their size and maturation, supporting a role for free radicals in the teratogenic effects of diabetes.

3-Hydroxybutyric Acid↗
PubMed1996

In vitro effects of a flavonoid-rich extract on LDL oxidation.

Flavonoids are phenolic compounds of vegetable origin with antioxidant effects. The present study aimed to determine their properties as LDL antioxidants. LDL were incubated with increasing concentrations of flavonoids (0-16 micrograms/ml) and LDL oxidation was started by adding CuCl2 (2 microM) to the media. When flavonoids were present in the media, vitamin E consumption, the lag phase of conjugated diene formation, LDL electrophoretic mobility in agarose gels and the appearance of thiobarbituric acid reacting substances (TBARS) were delayed in a concentration-dependent manner. To determine whether flavonoids could terminate LDL oxidation once initiated, two sets of experiments were performed. In the first, LDL oxidation was initiated as described above. At 2 or 4 h of incubation, flavonoids were added (4 micrograms/ml) and their effect compared to samples where butylated hydroxytoluene or EDTA were added. At 5 h, in the LDL samples where flavonoids were added, the electrophoretic mobility and TBARS production were the same as those present in LDL samples incubated for the whole period in the absence of flavonoids. However, when either butylate hydroxytoluene or EDTA was added, as would be expected, the LDL oxidation process was completely arrested as shown by a reduction in the appearance of TBARS and a lower LDL electrophoretic mobility. In the second experiment, LDL oxidation was initiated as described above and at 0, 10 and 20 min, flavonoids were added (4 micrograms/ml). When vitamin E was still present in the LDL solution, the flavonoids were able to both increase the lag phase in the formation of conjugated dienes and to delay the consumption of vitamin E. The present results show that in vitro, flavonoids prevent LDL oxidation in a concentration-dependent manner, delaying the consumption of vitamin E, but they cannot terminate or delay LDL oxidation once vitamin E in LDL is consumed.

Antioxidants↗
PubMed1996

A sucrose-rich diet affects triglyceride metabolism differently in pregnant and nonpregnant rats and has negative effects on fetal growth.

A sucrose-rich diet (SRD) causes hypertriglyceridemia in nonpregnant rats. To determine whether a SRD further enhances gestational hypertriglyceridemia, female rats were divided into the following two groups: 1) rats fed a SRD (63 g sucrose/100 g), and 2) rats that received the same diet except that the sucrose was replaced by an equal amount of cornstarch (CD). Half of the rats were mated and studied at d 20 of gestation. Body weight increase did not differ between virgin rats fed either diet, but the final body weight of pregnant rats fed SRD was lower than that of rats fed CD due to fewer fetuses per litter and lower fetal and placental weights. The SRD enhanced plasma glucose and insulin concentrations in virgin but not in pregnant rats; plasma triglycerides and FFA concentrations and the rate of triglyceride secretion into the plasma were higher in pregnant than in virgin rats fed SRD, but the increase in liver triglycerides due to SRD was higher in virgin rats. Both removal rate of a fat emulsion and adipose tissue lipoprotein lipase activity (LPL) were lower in virgin rats fed SRD than in those fed CD. They were lower in pregnant than in virgin rats fed CD. Placental and fetal liver triglyceride concentration and placental LPL were higher in rats fed SRD than in those fed CD. Both the increased triglyceride secretion by the liver and the decreased triglyceride removal from blood resulting in maternal hypertriglyceridemia may contribute to the negative effect of SRD on the developing fetus.

Adipose Tissue↗
PubMed1996

Effect of diabetes on protein synthesis rate and eukaryotic initiation factor activities in the liver of virgin and pregnant rats.

To study the effect of prolonged diabetes on protein synthesis and on the activities of initiation factors eIF-2 and eIF-2B in the liver, female rats were treated with streptozotocin. Some animals were mated and studied on day 20 of pregnancy, whereas others were kept virgin and studied in parallel. The protein synthesis rate was measured with an "in vitro' cellfree system, and was lower in diabetic pregnant and virgin animals than in pregnant and virgin controls (30-60%). The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they always showed a higher protein synthesis rate than their mothers or virgin rats. Protein synthesis rate, RNA concentration, and initiation factor 2 activity were higher in pregnant than in virgin rats. Both activity and level of eIF-2 factor changed in parallel to the protein synthesis rate, although no differences could be detected between control and diabetic animals. The eIF-2B activity in tissue extracts from diabetic virgin rats and fetuses was lower than in extracts from their controls, whereas no differences could be detected between pregnant and virgin control rats nor between pregnant control and pregnant diabetic animals. The percentage of the phosphorylated form of eIF-2 factor, eIF-2(alpha P), was slightly lower in virgin than in pregnant rats but was unaffected by the diabetic condition, while in diabetic fetuses this parameter was lower than in their corresponding controls. The cyclic adenosine monophosphate dependent protein kinase level was lower in diabetic rats than in controls, whereas no changes in the activity of casein kinase II were found. The isoelectric forms of the beta subunit of eIF-2 factor, eIF-2 beta, were different in the diabetic and the control animals, indicating that insulin deficiency modifies the phosphorylation of specific substrates. Since no differences were detected in RNA or eIF-2 content between control and diabetic rats, translation may, at least partly, be inhibited in the liver by an impairment of peptide chain initiation caused by the decreased eIF-2B activity which nevertheless is independent of eIF-2 alpha phosphorylation.

Animals↗
PubMed1996

Fatty acid composition of lipoprotein lipids in hepatobiliary diseases.

Liver damage and alterations in the exocrine function of the gland lead to a profound alteration of the plasma lipoprotein profile. To determine whether hepatic disease results in changes in the lipoprotein fatty acid composition, i.e. to determine whether liver function influences the homeostasis of complex lipids in plasma, we studied the fatty acid profile of lipids from VLDL, LDL and HDL, as well as from total plasma, in thirty-one patients of both sexes with hepatobiliary pathology (compensated liver cirrhosis, uncompensated liver cirrhosis, primary biliary cirrhosis, other intrahepatic cholestasis, and acute viral hepatitis). We also studied a group of healthy adults as controls. We present the lipoprotein profile and the fatty acid composition (myristic C14, palmitic C16, palmitoleic C16: 1, stearic C18, oleic C18: 1, linoleic C18: 2, eicosatrienoic C20: 3 omega 6 and arachidonic C20: 4) of lipoprotein and total plasma triacylglycerols, cholesteryl esters and phospholipids. The main observation of this study is that, despite the profound changes in the lipoprotein profile and the lower abundance of polyunsaturated fatty acids in complex lipids, the composition of all triacylglycerols, cholesteryl esters and phospholipids is very similar for the corresponding lipoproteins of patients with hepatobiliary disease and of control subjects. This indicates that in the controls as in the studied patients, the exchange of lipids between plasmatic lipoproteins is very rapid and demonstrates the possible importance of the extrahepatic synthesis of cholesteryl ester transfer protein.

Adult↗
PubMed1995

Effect of streptozotocin diabetes on polysomal aggregation and protein synthesis rate in the liver of pregnant rats and their offspring.

To study the effect of diabetes on hepatic protein synthesis and polysomal aggregation in pregnant rats, female rats were treated with streptozotocin prior to conception. Some animals were mated, and studied at day 20 of pregnancy, whereas, others were studied in parallel under non pregnant conditions. The protein synthesis rate measured with an "in vitro" cell-free system was higher in pregnant than in virgin control rats. It decreased with diabetes in both groups, although values remained higher in diabetic pregnant rats than in the virgin animals. The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they showed a higher protein synthesis rate than either their respective mothers or virgin rats. Liver RNA concentration was higher in control and diabetic, pregnant rats than in virgin rats, and the effect of diabetes decreasing this parameter was only significant for pregnant rats. Liver RNA concentration in fetuses was lower than in their mothers, and did not differ between control and diabetic animals. The decreased protein synthesis found in diabetic animals was accompanied by disaggregation of heavy polysomes into lighter species, indicating an impairment in peptide-chain initiation.

Animals↗
PubMed1995

Effect of etofibrate on bile production in the normolipidemic rat.

1. The effect of etofibrate, the ethandiol-1,2 diester of nicotinic and clofibric acids on bile production was studied in male rats that received a daily dose of 300 mg of etofibrate/kg body weight by stomach tube for 10 days and were compared with control rats receiving the medium. 2. The bile duct was cannulated, animals were intravenously given 1 microCi (4-14C)-cholesterol/100 b.w. and bile was collected at different intervals for a total of 4 hr. 3. Etofibrate treatment decreased plasma cholesterol and triglyceride concentrations and increased the bile flow. The cummulative amount of both bile volume and total bile radioactivity secreted increased linearly in all the animals; the respective slopes being higher in etofibrate treated rats than in controls. 4. The main labelled component found in the bile was always bile acids rather than cholesterol and the proportion of each of these compounds was similar in both groups. Neither was any difference between the groups found in the concentration of bile acids, cholesterol and phospholipids nor in the cholesterol/(bile+phospholipid) ratio. 5. Besides other factors, the present results indicate that an increase in bile flow and biliary cholesterol excretion in its free form and after its conversion into bile acids should contribute to the hypocholesterolemic effect of etofibrate.

Animals↗
PubMed1995

Sperm migration through the female genital tract of the New World monkey Cebus apella.

This study was designed to characterize sperm migration in the female genital tract of Cebus apella. Forty-eight cycles of eighteen females mated during the periovulatory period were studied. Eggs were searched for and spermatozoa were counted in segmental flushings of the genital tract performed in situ 1-7 h, 19-31 h, or 45-56 h after coitus. Of 14 eggs recovered, 8 were fertilized, thus assuring a reasonable normality of prefertilization phenomena in both males and females. A downward gradient of several orders of magnitude in sperm numbers was recognized from cervix to ampulla, particularly over the first interval. The population in the cervix and uterus decreased progressively between the first and last interval. Spermatozoa were recovered from the ampulla as early as 1 h after mating. Different trends were observed in the isthmus and ampulla. From the first to the last interval, sperm numbers decreased in the ampulla, but not in the isthmus. The number of spermatozoa recovered from the ampulla of the ovulatory side 1-31 h postcoitum was higher in postovulatory than in preovulatory monkeys, while in the nonovulatory side, recovery was similar in the two conditions. This findings suggests that the passage of spermatozoa up to the site of fertilization is under local control and is synchronized with ovulation. The pattern of sperm migration that emerges from these data bears similarities to the pattern in nonprimate species as well as distinctive features. A unique feature in common with the pattern in human is the early establishment of a fairly abundant and persistent sperm population in the ampulla.

Animals↗
PubMed1995

Reversion of insulin resistance in the rat during late pregnancy by 72-h glucose infusion.

To determine whether sustained exaggerated hyperinsulinemia in normoglycemic rats modifies insulin responsiveness during pregnancy, 17-day-pregnant and virgin rats were studied after receiving a continuous intravenous infusion (35 ml/day) of either 50% glucose or bidistilled water (controls) for 72 h. Plasma glucose was unchanged, whereas insulin was highly increased, and the effect was more marked in pregnant than in virgin rats. Insulin responsiveness, estimated under the hyperinsulinemic euglycemic clamp with 0.8 IU insulin.h-1.kg-1, was lower in control pregnant than in virgin rats but higher in pregnant than in virgin rats in those that had received the glucose infusion. The tissue glucose utilization metabolic index (GUI) was estimated with 2-deoxy-D-[1-3H]glucose in the clamped rats. The GUI was lower in heart, white- and red-fiber skeletal muscle, and adipose tissue in control pregnant rats than in control virgin rats, and, although the glucose infusion decreased that index in both red-fiber muscle and adipose tissue in virgin rats, glucose increased the index in red-fiber muscle in pregnant rats to the level found in virgin controls. Results therefore show that, when unaccompanied by hypoglycemia, sustained exaggerated hyperinsulinemia decreases insulin responsiveness in virgin rats but reverts insulin resistance in late-pregnant rats.

Animals↗
PubMed1995

Glucose and insulin tolerance tests in the rat on different days of gestation.

To study insulin/glucose relationship during gestation, rats were studied on days 6, 12, 15, 18, 20 or 21 of pregnancy and the results were compared to values in sex-matched virgin control rats. Blood glucose levels were decreased on days 20 and 21 of gestation whereas plasma insulin levels appeared decreased on days 6 and 12, unchanged on day 15 and enhanced on days 18, 20 and 21 of gestation. Total pancreas insulin content was already augmented on day 6 of gestation and continued to increase with gestational time. With the exception of an increase in the 6-day-pregnant rats 22.5 min after an oral glucose load, blood glucose levels did not differ between 6- or 12-day-pregnant rats and virgin controls although plasma insulin levels reached higher values on these days. However, in the 15-day-pregnant rats, glucose tolerance after the glucose load was enhanced while plasma insulin levels did not differ from those in virgin rats during the first 30 min. In the 18-day-pregnant rat blood glucose was more increased but plasma insulin did not differ after the glucose load when compared to virgin rats, whereas 20- or 21-day-pregnant rats showed a glucose tolerance similar to that of virgin rats but their insulin levels shortly after the glucose load were higher. The hypoglycemic response to a high intravenous dose of insulin was decreased in 12-, 18-, 20- and 21-day-pregnant rats. Therefore, whereas in both the 6- and 12-day-pregnant rats there is an enhanced beta-cell response to the glucose insulinotropic effect and insulin responsiveness is reduced in 12-day-pregnant rats, the 15-day pregnant rat is in a transitory stage where both insulin sensitivity and the beta-cell response return to nonpregnant values. However, from 18 days of gestation on, there is an intense insulin-resistant condition which is only partially compensated by an enormous accumulation of insulin in the pancreas followed by a faster and larger insulin release after a glucose load.

Animals↗
PubMed1994

Effect of starvation on lipoprotein lipase activity in different tissues during gestation in the rat.

This study was addressed to determine whether the tissue-specific LPL activity response to fasting differs between nonpregnant and pregnant rats over the course of pregnancy. Fed and 24-h fasted rats were studied at days 12, 15 or 20 of gestation and were compared to virgin controls. In fed rats at days 15 and 20 of gestation LPL activity decreased in lumbar adipose tissue and the heart and liver, and increased in mammary gland tissue. Fasting decreased LPL activity in lumbar adipose tissue in 12 day pregnant and virgin rats and in mammary gland tissue in pregnant rats at 15 and 20 days of gestation and in virgin rats, whereas it increased LPL activity in heart tissue in rats at day 15 and 20 and in liver at day 20 of gestation. Plasma triacylglycerols were higher in 20 day pregnant rats than in the other groups when fed and this difference was even more noticeable in the fasting condition where the plasma beta-hydroxybutyrate level also reached the highest value in the 20 day pregnant rats. Since tissue LPL activity controls the hydrolysis and uptake of circulating triacylgylcerols, the present results indicate that in fed rats after the 15th day of gestation circulating triacylglycerols are preferentially taken up by the mammary gland instead of being taken up by adipose tissue and heart. However, after fasting, circulating triacylglycerols are driven to the heart and liver in the late pregnant rat, and become a major source for fatty acid oxidation, an effect that seems to be specially evident in the liver of the 20 day pregnant rat where there is an intense increase in LPL activity and the triacylglycerols become preferential substrates for ketone body production.

3-Hydroxybutyric Acid↗
PubMed1994

[Changes in the lipid profile in chronic hepatopathies].

BACKGROUND: The pattern of lipoproteins and apolipoproteins has been studied in a group of patients with chronic liver disease. The differences in this pattern were analysed in relation with the stage of liver disease and the presence of cholestasis. METHODS: Twenty one patients with hepatic cirrhosis and 12 with primary biliary cirrhosis were studied. Two subgroups were established according to the disease severity and to the Scheuer classification, respectively. Plasma lipoproteins were separated by ultracentrifugation, and the lipid and apolipoprotein composition were determined. Lipoprotein X was identified by means of agarose gel electrophoresis. RESULTS: In the subgroups with less severe liver disease, only minimal changes were found, such as the decreases in esterified cholesterol and Apo E contents in VLDL in the cirrhotic patients, and the increase of HDL-cholesterol in the patients with primary biliary cirrhosis in the first stages. In patients with severe hepatic cirrhosis, total esterified cholesterol, triglycerides, VLDL and HDL were diminished. Apo E in VLDL was undetectable whereas the different Apo C isoforms were in the normal proportion. Patients with severe biliary cirrhosis showed high levels of total cholesterol and triglycerides, elevated LDL-cholesterol, and decreased HDL-cholesterol and total esterified cholesterol. Apo C-IIO in VLDL was proportionally increased as related to both Apo E and Apo C-III. Lipoprotein X was detected in all these patients and in half of the patients with severe hepatic cirrhosis. CONCLUSIONS: Severe chronic liver disease is associated with a decrease of the concentration of hepatic lipoproteins and the absence of Apo E in VLDL, probably as a result of a defect in their synthesis. The lipid profile found in patients with biliary cirrhosis delineates the pattern of chronic cholestasis, which is characterized by the presence of lipoprotein X, a significant increase of free-cholesterol and a decrease of HDL-cholesterol; VLDL, which are increased, are rich in Apo C-II. Data show the distinct apolipoprotein composition of VLDL in the different hepatic diseases.

Adult↗
PubMed1994

Changes in cholesteryl ester transfer protein activity during normal gestation and postpartum.

Cholesteryl ester transfer protein (CETP) activity was measured in a d > 1.21 kg/L plasma fraction collected from healthy women at different times during gestation, postpartum, and in control women. CETP activity was highest in the second trimester of gestation, declined at the third trimester, and was lowest at postpartum. Only the value at the second trimester was significantly different from that of control women. This trend differed from that of circulating lipoproteins: very low-density lipoprotein (VLDL)-lipids, including triglycerides and cholesterol, increased progressively from the first to the third trimester, and then declined at postpartum. Low-density lipoprotein (LDL)-cholesterol levels, like VLDL levels, rose during gestation but then remained elevated at postpartum. High-density lipoprotein (HDL)-cholesterol as well as HDL-phospholipids and apolipoprotein A-I, peaked in the second trimester, remaining elevated in the third trimester and then fell at postpartum. Finally, HDL-triglyceride increased markedly from the first to the second trimester, rose somewhat higher during the third trimester, and declined at postpartum. When all the samples from pregnant women were considered together, CETP activity correlated significantly with HDL-triglyceride levels and the changes in CETP activity during gestation and postpartum paralleled those of the HDL-triglyceride/VLDL-triglyceride ratio. These results suggest that CETP contributes to the exaggerated accumulation of triglycerides in HDL that begins in the second trimester of human gestation.

Adult↗
PubMed1994

Lipoprotein lipase and hormone-sensitive lipase activity and mRNA in rat adipose tissue during pregnancy.

To investigate the factors controlling maternal depot fat accumulation during early pregnancy and net decrease during late pregnancy, the activity and mRNA expression of adipose tissue lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) were related to several other lipid metabolic parameters. Virgin control rats, pregnant rats (at days 12, 15, 19, and 21), and lactating rats (at days 5 and 10 postpartum) were studied. In adipose lumbar tissue of late pregnant rats, LPL activity decreased to about one-third that of the virgin control animals, with < 10% of initial LPL mRNA expressed as determined by Northern blots. HSL activity increased maximally 1.5-fold with a fourfold increase of HSL expression at days 12-15 of pregnancy and decreased to control levels after parturition. The HSL-to-LPL mRNA and activity ratios were enhanced from days 15 and 19 of pregnancy, respectively, and remained so even during lactation, mainly because of the marked lowering of the LPL values. This enhancement coincided with increments in plasma free fatty acids and glycerol levels indicating an increased depot fat breakdown. These results give no indication of an involvement of LPL and HSL gene expression changes in the accumulation of maternal depot during early pregnancy. In contrast, such changes could be responsible for the net breakdown of this fat depot during late gestation. Thus, during this physiological state, long-term (e.g., transcriptional) regulation of LPL and HSL gene expression could be an important mechanism for the control of adipose tissue mass breakdown during late gestation.

Adipose Tissue↗
PubMed1994

Carbohydrate-lipid interactions during gestation and their control by insulin.

1. 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 nutrients when she eats. During this phase maternal fat deposits are accumulated thanks to the enhancement in adipose tissue lipogenic and glycerologenic activity. In contrast, in the latter part of gestation, the rapid fetal growth is sustained by the intense transfer of nutrients from maternal circulation. 2. Glucose is quantitatively the most abundant of the several substrates that cross the placenta and despite increased maternal gluconeogenesis this transfer is responsible for the maternal tendency to hypoglycemia. This causes a switch to a net catabolic state which is especially evident in the net breakdown of fat depots. 3. Enhanced release of adipose tissue lipolytic products, free fatty acids (FFA) and glycerol, facilitates the liver synthesis of triglycerides and their later release into circulation associated to very low-density lipoprotein (VLDL). Glycerol is also used as an important gluconeogenic substrate and FFAs are broken down through beta-oxidation for ketone body synthesis. Flow through these pathways becomes increased when food is withheld and this actively contributes to the availability of fuels to the fetus which becomes partially preserved from maternal metabolic insult. Increased 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. 4. While the maternal anabolic tendencies found during the first two-thirds of gestation seem to be facilitated by hyperinsulinemia in the presence of a normal responsiveness to the hormone, it is proposed that most of the metabolic changes taking place during the last third of gestation seem to be caused by the insulin-resistant state which is consistently present at this stage, since its reversion caused by sustained exaggerated hyperinsulinemia also reverts several of these metabolic adaptations.

Adipose Tissue↗