In vitro effects of 1-(4-dimethylaminobenzylidene)-2-(2-hydroxybenzylidene) hydrazine and its copper complex on lymphocyte proliferation and function in the presence of free radical generator.

In this study, the in vitro effects of 1-(4-dimethylaminobenzylidene)-2-(2-hydroxybenzylidene) hydrazone (L1) and its corresponding copper complex [Cu(L1)], synthesized in our laboratory, were investigated on the proliferative responses, Th1 (interleukin-2 (IL-2), interferon-γ (INFγ)) and Th2 (IL-4) cytokine secretion, adenosine triphosphate (ATP) levels and intracellular redox status of T lymphocytes submitted to H2O2/FeSO4-mediated oxidative stress. T cells were isolated on histopaque density gradient by differential centrifugation, and were cultured with the mitogen concanavalin A (Con A), free radical generator (H2O2/FeSO4) and with different concentrations of L1 and [Cu(L1)] (1 - 100 µM). Proliferation (MTT assay), cytokines (Elisa kits), ATP levels, cytotoxic effect (micronucleus test) and oxidative markers (glutathione, catalase, superoxide dismutase, hydroperoxide and carbonyl protein contents) were investigated after 48-h incubation. Our results showed that H2O2/FeSO4 treatment induced a reduction in T lymphocyte proliferation, cytokine secretion and ATP levels associated to an evident intracellular oxidative stress, inflammatory profile and DNA damage. Addition of L1 at 100 µM was able to increase cell proliferation, IL-2, IL-4 and INFγ secretion and ATP contents and to reduce hydroperoxide and carbonyl protein contents, catalase activity and micronuclei number in lymphocytes under oxidative stress, with a partial protection. The [Cu(L1)] exhibited protective effects in T lymphocytes by inhibiting H2O2/FeSO4 - induced cell proliferation suppression, inflammatory status, ATP loss and oxidative stress generation, whatever the concentration used. In conclusion, in the situation of excessive oxidative stress, [Cu(L1)] treatment improved T lymphocyte proliferation, cytokine production, ATP contents and oxidant/antioxidant status. [Cu(L1)] could be effective at improving oxidative stress and T cell abnormalities.

[Effect of N-3 polyunsaturated fatty acids on the modulation of T lymphocytes in vitro and redox status in obese women with hypertension]. / Effet des acides gras polyinsaturés N-3 sur la modulation in vitro des lymphocytes T et le statut redox chez les femmes obèses hypertendues.

OBJECTIVES: Deepen our knowledge of the immune system alterations associated with obesity-related hypertension and demonstrate that polyunsaturated fatty acids can enhance the proliferation and their profile oxidant/antioxidant and subsequently involved in the strategy prevention and treatment in obese hypertensives. METHODS: T cells are isolated from the blood of the control and obese women with hypertension the University Hospital of Tlemcen (Algeria), these cells are incubated in the presence of a synthetic mixture of PUFA to 30µM (DHA/EPA/LA) and stimulated by mitogens for 48hours. The cells are counted and used to assess intracellular oxidative status. The biochemical parameters are determined by the use of plasma. RESULTS: In obese women with hypertension, a significant increase in plasma levels of (glucose, uric acid, creatinine, urea, total cholesterol and triglycerides) compared to controls. In addition, decreased cell proliferation, basal or stimulated by Con A was observed in obese women with hypertension compared with controls. The mixture of PUFA to 30µM reduced lymphoproliferation as well in obese women with hypertension than in controls. The rates in malondialdéhyde (MDA) and protein carbonyl lymphocytes are elevated in hypertensive obese women. PUFA supplementation to 30µM seems correct this redox status in hypertensive obese since rates in protein carbonyl, are similar to those of controls. CONCLUSION: The mixture of PUFA (n-3 and n-6) can modulate the activity of T lymphocyte proliferation and correct the intracellular redox status in hypertensive obese women.

Effect of dietary n - 3 polyunsaturated fatty acids on oxidant/antioxidant status in macrosomic offspring of diabetic rats.

The aim of this work was to determine the effect of dietary n - 3 PUFA on oxidant/antioxidant status, in vitro very low and low density lipoprotein (VLDL-LDL), and VLDL-LDL-fatty acid composition in macrosomic pups of diabetic mothers. We hypothesized that n - 3 PUFA would improve oxidative stress in macrosomia. Diabetes was induced in female Wistar rats fed with the ISIO diet (control) or with the EPAX diet (enriched in n - 3 PUFAs), by streptozotocin. The macrosomic pups were killed at birth (day 0) and at adulthood (day 90). Lipid parameters and VLDL-LDL-fatty acid composition were investigated. The oxidant/antioxidant status was determined by measuring plasma oxygen radical absorbance capacity (ORAC), hydroperoxides, carbonyl proteins, and VLDL-LDL oxidation. Macrosomic rats of ISIO fed diabetic mothers showed an increase in plasma and VLDL-LDL-triglycerides and VLDL-LDL-cholesterol levels and altered VLDL-LDL-fatty acid composition. Plasma ORAC was low with high hydroperoxide and carbonyl protein levels. The in vitro oxidizability of VLDL-LDL was enhanced in these macrosomic rats. The EPAX diet corrected lipid parameters and improved oxidant/antioxidant status but increased VLDL-LDL susceptibility to oxidation. Macrosomia is associated with lipid abnormalities and oxidative stress. n - 3 PUFA exerts favorable effects on lipid metabolism and on the oxidant/antioxidant status of macrosomic rats. However, there are no evident effects on VLDL-LDL oxidation.

Oxidative stress and maternal obesity: feto-placental unit interaction.

OBJECTIVE: To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. PATIENTS AND METHODS: 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. RESULTS: Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. DISCUSSION: Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. CONCLUSION: Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered.

5,6-dihydro-2H-pyranones and 5,6-dihydro-2H-pyridones and their derivatives modulate in vitro human T lymphocyte function.

The aim of this work was to study the in vitro effects of δ-lactone 1, δ-lactam 3 and their enaminone derivatives 2 and 4, synthesized in our laboratory, on the proliferative responses of human lymphocytes, Th1 and Th2 cytokine secretion and intracellular redox status. Peripheral blood lymphocytes were isolated using differential centrifugation on a density gradient of Histopaque. They were cultured with mitogen concanavalin A (Con A) and with different concentrations of the compounds 1, 2, 3 and 4 (0.1-10 µM). Proliferation (MTT assay), IL-2, INFγ and IL-4 (Elisa kits), oxidative markers (intracellular glutathione, hydroperoxide and carbonyl protein contents) and cytotoxic effect (micronucleus test) were determined. The compounds 1 and 2 are immunosuppressive and decrease IL-2, INFγ and IL-4 secretion with a shift away from Th2 response to Th1 phenotype. The compounds 3 and 4 were immunostimulant and increased cytokine secretion with a shift away from Th1 response to Th2. The introduction of an enamine group to 1 and 3 to provide 2 and 4 seemed to attenuate their immunological properties. These immunomodulatory properties were, however, accompanied by an increase in lymphocyte intracellular oxidative stress, especially with 1 and 2 at high concentrations. In conclusion, the compounds 1, 2, 3 and 4 could be used to provide cell-mediated immune responses for novel therapies in T-cell mediated immune disorders.

Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: a comparison of older with young men.

In this study, plasma lipids, lipoproteins and markers of oxidant/antioxidant status were investigated in young (n = 45) and older (n = 40) obese men and compared to those in young (n = 65) and older (n = 55) normal weight controls. The purpose was to determine whether obesity exacerbates or not lipid, lipoprotein abnormalities and oxidative stress in older men. Our findings showed that all obese patients had increased plasma triglyceride, cholesterol, LDL-cholesterol, -triglyceride and HDL-triglyceride levels concentrations compared to controls (P < 0.01). However, the younger obese men had relatively larger and accentuated changes in plasma lipids and lipoproteins than the older patients. Additionally, total antioxidant capacity (ORAC), vitamins C and E were lower while hydroperoxides and carbonyl proteins were higher in young and older obese patients compared to their respective controls (P < 0.001). Erythrocyte antioxidant SOD and catalase activities were enhanced in obese young patients, but reduced in obese older men. Glutathione peroxidase activity was low in obesity irrespective of age. In multiple regression analysis, BMI significantly predicted total cholesterol, LDL-C, LDL-TG and HDL-TG (P < 0.0001). These relationships were not modified by age. BMI alone was a not a significant predictor for ORAC, vitamins C, E, catalase and Glutathione peroxidase. However, the interaction BMI-age significantly predicted these parameters and explained 28-45% of their changes. BMI was a significant predictor of SOD, carbonyl proteins and hydroperoxides. This effect became more significant (P < 0.0001) and worsened with BMI-age interaction. In conclusion, lipoprotein metabolism and oxidant/antioxidant status are altered in obesity irrespective of age. However, obesity-related lipid and lipoprotein alterations were attenuated while oxidative stress was aggravated in older adults.

Serum lipoprotein composition, lecithin cholesterol acyltransferase and tissue lipase activities in pregnant diabetic rats and their offspring receiving enriched n-3 PUFA diet.

The effects of dietary n-3 polyunsaturated fatty acids on lipoprotein concentrations and on lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL) and lecithin cholesterol acyltransferase (LCAT) activities were studied in streptozotocin-induced diabetic rats during pregnancy and in their macrosomic offspring from birth to adulthood. Pregnant diabetic and control rats were fed Isio-4 diet (vegetable oil) or EPAX diet (concentrated marine omega-3 EPA/DHA oil), the same diets were consumed by pups at weaning. Compared with control rats, diabetic rats showed, during pregnancy, a significant elevation in very low density lipoprotein (VLDL) and low and high density lipoprotein (LDL-HDL(1))-triglyceride, cholesterol and apoprotein B100 concentrations and a reduction in apoprotein A-I levels. HTGL activity was high while LPL and LCAT activities were low in these rats. The macrosomic pups of Isio-4-fed diabetic rats showed a significant enhancement in triglyceride and cholesterol levels at birth and during adulthood with a concomitant increase in lipase and LCAT activities. EPAX diet induces a significant diminution of VLDL and LDL-HDL(1) in mothers and in their macrosomic pups, accompanied by an increase in cholesterol and apoprotein A-I levels in HDL(2-3) fraction. It also restores LPL, HTGL and LCAT activities to normal range. EPAX diet ameliorates considerably lipoprotein disorders in diabetic mothers and in their macrosomic offspring.

Serum lecithin: cholesterol acyltransferase activity, HDL2 and HDL3 composition in hypertensive mothers and their small for gestational age newborns.

The aim of this study was to determine serum lecithin:cholesterol acyltransferase (LCAT) activity in parallel with HDL2 and HDL3 amounts and composition in pregnancy induced hypertension (PIH) and chronic hypertensive (CH) mothers and in their small for gestational age (SGA) newborns. LCAT activity was assayed by conversion of [3H] cholesterol to labelled cholesteryl ester. HDL2 and HDL3 were separated by ultracentrifugation. At term, cholesterol values were similar in PIH, CH and controls. However, higher levels of triglycerides were observed in PIH and CH (+20% and +21%, respectively) as compared with normotensive control mothers (NC). HDL2 and HDL3-phospholipids, HDL2-cholesterol concentrations and LCAT activity were lower in PIH and CH mothers than in NC mothers. Similar changes were also observed in SGA newborns of PHI mothers and in SGA newborns of CH mothers when compared to appropriate for gestational age newborns of control mothers (AGA-NC). In addition, SGA newborns showed low HDL2 and HDL3 apoA-I contents. Maternal hypertension and foetal intrauterine growth retardation are associated with profound abnormalities in HDL metabolism, consistent with an atherogenic risk. SGA lipoprotein profiles appear to implicate later metabolic diseases.

[2-hydroxy-methyl-1(N-phtaloyltryptophyl) aziridine stimulates in vitro human lymphocyte proliferation and interleukin secretion]. / 2-hydroxy-methyl-1(N-phtaloyltryptophyl) aziridine stimule la prolifération in vitro des lymphocytes humains et la sécrétion des interleukines.

UNLABELLED: AIM OF THIS WORK: Aziridines have been shown to possess marked immunotropic activity. In this study, the in vitro effects of a new aziridine, 2-hydroxy-methyl-1-(N-phtaloyltryptophyl) aziridine, were determined on the proliferative responses of human lymphocytes stimulated by mitogens and on interleukin (IL-2, IL-6) secretion. MATERIAL AND METHODS: Peripheral blood lymphocytes were isolated using differential centrifugation on a density gradient of Ficoll-Paque. They were cultured with or without mitogens (Concanavalin A and lipopolysaccharide), and with different concentrations of the aziridine. Proliferation was monitored by direct cell counts and confirmed by MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. After different incubations, IL-2 and IL-6 were determined by using commercially available Elisa kits. RESULTS: The aziridine tested significantly stimulated the resting and mitogen T and B lymphocyte proliferation at concentrations between 1 microM and 1 mM, in a dose-dependent manner. It also increased IL-2 and IL-6 secretion. CONCLUSION: 2-hydroxy-methyl-1-(N-phtaloyltryptophyl) aziridine displayed immunomodulatory properties and is potentially immunostimulant. It could be used to provide non-specific cell-mediated immune responses.

N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring.

OBJECTIVE: We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring. DESIGN: Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days. MEASUREMENTS: Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined. RESULTS: Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals. CONCLUSION: Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.

Effects of N-acyl-2-hydroxymethyl aziridines on in vitro proliferative responses of human lymphocytes stimulated by mitogens.

Aziridines have been shown to possess marked immunotropic activity. The aim of this work was to study the in vitro effects of different concentrations of three novel aziridines, 2-hydroxy-methyl-1-(N-phtaloylglycyl) aziridine (aziridine 1), 2-hydroxy-methyl-1-(N-phtaloylalanyl) aziridine (aziridine 2) and 2-hydroxy-methyl-1-(N-phtaloylphenylalanyl) aziridine (aziridine 3), on the proliferative responses of human lymphocytes stimulated by mitogens (concanavalin A (Con A) and lipopolysaccharide (LPS)), and interleukin-2 (IL-2), interleukin-6 (IL-6) secretion. The results showed that aziridines 1 and 3 significantly stimulated the resting and Con A or LPS lymphocyte proliferation at concentrations between 1 micromol/l and 1 mmol/l, in a dose-dependent manner, the action of aziridine 3 being the highest. They also increased IL-2 and IL-6 secretion. However, aziridine 2 had no effect on the resting lymphocyte proliferation in the absence of mitogens, at any concentration used, reduced Con A-stimulated T lymphocyte proliferation and LPS- stimulated B lymphocyte proliferation in a dose dependent manner and diminished IL-2 and IL-6 production. None of the three aziridines affected cell viability. In conclusion, the three aziridines used in this study displayed immunomodulatory properties. Aziridines 1 and 3 are potentially immunostimulant while aziridine 2 is immunosuppressive and could be used to provide nonspecific cell-mediated immune responses.

Impaired oxidant/antioxidant status and LDL-fatty acid composition are associated with increased susceptibility to peroxidation of LDL in diabetic patients.

This study was carried out to determine the relationships between oxidant/antioxidant status, in vitro LDL oxidizability and LDL-fatty acid composition in diabetes mellitus. Plasma total antioxidant capacity (oxygen radical absorbance capacity, ORAC) and LDL-cholesteryl ester fatty acids were investigated in type 1 and type 2 diabetic subjects with and without complications. The degree of LDL oxidation was determined by the measurement of hydroperoxide levels before and after in vitro peroxidative stress with CuSO4. ORAC values were decreased in diabetic subjects who showed high basal hydroperoxide levels. Oxidizability of LDL in these subjects was higher than in control subjects and it was unrelated to LDL-fatty acid composition. However, in type 2 diabetic subjects with complications, alterations in LDL-fatty acid composition were associated with their enhanced oxidative susceptibility. LDL-fatty acid alterations might be an additional factor that influences LDL oxidizability especially in type 2 diabetes. In conclusion, diabetes mellitus is associated with enhanced oxidative stress and defective antioxidant/oxidant balance regardless the type of diabetes and presence of complications.

Antioxidant status and levels of different vitamins determined by high performance liquid chromatography in diabetic subjects with multiple complications.

Plasma vitamin A, C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications, i.e., hypertension, coronary artery disease and renal failure. Reverse phase HPLC was used to quantify vitamin A and E levels. We observed that the vitamin C levels were not significantly different between control and diabetic subjects. However, vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls. Superoxide dismutase (SOD) activity was significantly lower in type II, but not in type I, diabetic patients compared to controls. Interestingly, glutathione reductase and peroxidase activities were diminished in type I, but not in type II, diabetic subjects as compared to controls. Catalase activity was lower in both types of diabetic patients in comparison with their respective controls. Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications.

Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes.

The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL(1), and HDL(2-3) cholesterol levels (P < 0.05) associated with increased LCAT activity (+57%) compared with control values. At 1 and 2 months of life, serum and lipoprotein cholesterol concentrations in macrosomic rats were similar to those of controls, whereas LCAT activity remained elevated about 1.5-fold. In addition, there was no change in hepatic cholesterol contents but hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT activities were higher in both macrosomic males and females than in their respective controls (P < 0.01). By 3 months, macrosomic rats had developed hypercholesterolemia with a rise in all lipoproteins. Enzyme activities were still increased in these mature macrosomic rats, and hepatic cholesteryl esters were higher only in macrosomic females. These data demonstrate an overproduction, combined with overutilization, of cholesterol during the phase of rapid growth in macrosomic rats. However, cholesterol oversynthesis exceeded its removal and was a major contributor to hypercholesterolemia in adult macrosomic rats. In conclusion, macrosomia was associated with alterations in cholesterol metabolism through adulthood.

Maternal and fetal serum lipid and lipoprotein concentrations and compositions in type 1 diabetic pregnancy: relationship with maternal glycemic control.

The aim of this study was to determine maternal and fetal lipoprotein profiles in type 1 diabetic pregnancies differing in glycemic control. Serum lipid, apolipoprotein, and lipoprotein lipid concentrations were investigated in mothers with poorly controlled or well-controlled type 1 diabetes as reflected by hemoglobin A1c(HbA1c) concentrations performed by isolab column chromatography and in their macrosomic (body wt = 4650 +/- 90 g) or appropriate-for-gestational-age newborns (body wt = 3616 +/- 68 g), and these levels were compared with those in healthy mothers and in their control newborns (body wt = 3290 +/- 45 g). In mothers with well-controlled diabetes and in their infants, serum lipid, apolipoprotein, and lipoprotein lipid concentrations were comparable to those in control mothers and in their control newborns. Mothers with poorly controlled diabetes presented higher serum triglyceride and apoprotein B-100 (apo B-100) levels but lower apo A-I and HDL3 cholesterol and phospholipid levels as compared with control values. In their macrosomic newborns, all serum lipid, apolipoprotein, and lipoprotein lipid levels were higher than those in control newborns. Maternal HbA1c and triglyceride levels in late gestation were significant predictors of fetal lipids and lipoproteins in the poorly controlled diabetes group. In conclusion, when under good metabolic control, type 1 diabetes did not affect maternal and fetal lipid levels. However, when under poor metabolic control, type 1 diabetes is associated with maternal and fetal lipoprotein abnormalities.

Impaired serum lipids and lipoproteins in fetal macrosomia related to maternal obesity.

The aim of this work was to determine lipoprotein metabolism alterations in macrosomic newborns and to see whether these lipoprotein abnormalities are parallel or not to those found in their obese or nonobese mothers. Serum lipids, apo A-I, apo B100, lipoproteins (VLDL, LDL, HDL2, and HDL3), and LCAT activity were investigated in obese and nonobese mothers and cord blood of their macrosomic or appropriate-for-gestational-age (AGA) newborns. Serum and VLDL triglyceride concentrations were higher in obese mothers of AGA newborns than in nonobese mothers. Serum triglyceride, VLDL, and apo B100 levels were higher, while serum apo A-I and HDL2 cholesterol concentrations were lower in obese mothers of macrosomic newborns than in the other groups. In their macrosomic newborns, serum lipid, lipoprotein, apo B100, and apo A-I levels were higher as compared with those of other newborns. Macrosomic newborns of nonobese mothers had lipoprotein profiles similar to those in AGA newborns. LCAT activity was similar in both mother groups and in both newborn groups. In conclusion, maternal obesity and fetal macrosomia were associated with lipoprotein abnormalities consistent with high atherogenic risk.

Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition.

AIMS: To determine the effects of fetal macrosomia related to maternal type 1 diabetes on the lipid transport system. METHODS: Serum lipoprotein concentrations and composition and lecithin:cholesterol acyltransferase (LCAT) activity were investigated in macrosomic newborns (mean birth weight, 4650 g; SEM, 90) and their mothers with poorly controlled type 1 diabetes, in appropriate for gestational age newborns (mean birth weight, 3616 g; SEM, 68) and their mothers with well controlled type 1 diabetes, and macrosomic (mean birth weight, 4555 g; SEM, 86) or appropriate for gestational age (mean birth weight, 3290 g; SEM, 45) newborns and their healthy mothers. RESULTS: In mothers with well controlled type 1 diabetes, serum lipids, apolipoproteins, and lipoproteins were comparable with those of healthy mothers. Similarly, in their infants, these parameters did not differ from those of appropriate for gestational age newborns. Serum triglyceride, very low density lipoprotein (VLDL), apolipoprotein B100 (apo B100), and high density lipoprotein (HDL) triglyceride concentrations were higher, whereas serum apo A-I and HDL3 concentrations were lower in mothers with diabetes and poor glycaemic control than in healthy mothers. Their macrosomic newborns had higher concentrations in all serum lipids and lipoproteins, with high apo A-I and apo B100 values compared with appropriate for gestational age newborns. In macrosomic infants of healthy mothers, there were no significant differences in lipoprotein profiles compared with those of appropriate for gestational age infants. LCAT activity was similar in both groups of mothers and newborns. CONCLUSION: Poorly controlled maternal type 1 diabetes and fetal macrosomia were associated with lipoprotein abnormalities. Macrosomic lipoprotein profiles related to poor metabolic control of type 1 diabetes appear to have implications for later metabolic diseases.

Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes.

The aim of this investigation was to determine the time course of changes in serum glucose, insulin and lipid levels, as well as lipid and protein content and lipolytic activities in insulin target organs (liver, adipose tissue and muscle), in macrosomic offspring of streptozotocin-induced mildly hyperglycaemic rats. Food intake and nutritional efficiency were also evaluated. Mild hyperglycaemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups (birth weight >1.7 S.D. greater than the mean value for the control pups) had higher serum insulin, glucose and lipid levels than control pups. These macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight up to 12 weeks of age. These rats were not hyperphagic; however, they had higher food efficiency and fat storage capacity with higher adipocyte lipoprotein lipase activity, which contributed to persisting obesity. Hepatic lipase activity was increased in macrosomic rats at all ages. Moreover, macrosomia was associated with metabolic disturbances that varied according to age and sex. After 1 month, several alterations observed at birth had disappeared. Serum glucose, insulin and lipid levels in male and female macrosomic rats became similar to those of their respective controls. At 2 months of age, hepatic and serum triacylglycerol levels were higher in macrosomic females than in controls. By 3 months, macrosomic rats (both males and females) had developed insulin resistance with hyperinsulinaemia, hyperglycaemia, and higher serum and hepatic lipids. In conclusion, macrosomia was associated with alterations in glucose and lipid metabolism through to adulthood. It should be considered as an important potential risk factor for obesity and its metabolic complications.

Changes in serum lipid and lipoprotein concentrations and compositions at birth and after 1 month of life in macrosomic infants of insulin-dependent diabetic mothers.

The aim of this study was to determine whether macrosomia related to maternal diabetes alters lipoprotein metabolism and whether these abnormalities still persist or regress after 1 month of life. Serum lipoprotein compositions and concentrations as well as serum lipid fatty acid compositions were investigated in macrosomic infants (birth weight = 4840 +/- 105 g at term) of insulin-dependent diabetic mothers at birth and after 1 month of life, and were compared to those of control infants (birth weight = 3400 +/- 198 g at term) of healthy mothers. Compared to controls, at birth, macrosomic newborns had higher serum lipids, apolipoprotein A-I and B-100, and lipoprotein (very low density lipoprotein, low density lipoprotein, high density lipoprotein-2 and high density lipoprotein-3) levels. Higher percentages of C18:2n-6 in serum triacylglycerols, phospholipids and cholesteryl esters were also observed. At day 30, in macrosomics, serum triacylglycerol, apo B-100, very low density lipoprotein and low density lipoprotein levels were still significantly higher. C18:2n-6 and C18:3n-3 contents in serum phospholipids, triacylglycerols and cholesteryl esters were reduced while C20:4n-6 and C22:6n-3 contents in serum phospholipids and cholesteryl esters were enhanced, compared to control values. Macrosomia was associated with alterations in lipoprotein compositions and concentrations at birth, some of which persisted after 1 month of life, and might play a role in the pathogenesis of diabetes and atherosclerosis in adult life.

Low birth weight at term impairs cord serum lipoprotein compositions and concentrations.

UNLABELLED: The purpose of this study was to determine the effect of low birth weight at term on serum lipoproteins. Lipid and apolipoprotein (apo) contents were investigated in cord sera of small-for-gestational-age (SGA) newborns at term (2290 g +/- 33 g) and compared with those of appropriate-for-gestational-age (AGA) newborns (3570 g +/- 93 g). In SGA newborns, VLDL amounts were twofold higher, whereas LDL, HDL2 and HDL3 contents were lower than in AGA newborns (-38%, -44% and -42%, respectively). VLDL-triacylglycerols (TG), apo B-100 and apo E were higher, while VLDL-apo C-II values were 39% lower in SGA newborns compared with those of AGA newborns. In SGA newborns, HDL2-apolipoprotein, phospholipid and cholesteryl ester levels were respectively reduced to 70%, 50% and 40% compared with AGA values. HDL3-apolipoprotein and phospholipid contents were also decreased in SGA newborns (-43% and -60%, respectively). The different HDL2 and HDL3-apolipoproteins (apo A-I, A-II, C-III and E) were significantly decreased in SGA newborns. CONCLUSION: Intra-uterine growth retardation was accompanied by alterations in apolipoproteins and lipid compositions in the four lipoprotein fractions, which may impair lipid metabolism. Follow up studies on lipoprotein patterns in SGA infants are required to investigate whether such abnormalities at birth lead to diseases in adulthood.