Changes In Lipoprotein Lipase Activity Research Articles

Acute insulin response following exercise and its association to lipid changes in sedentary African-American women

Sedentary African-American (AA) women are at increased risk of hypertension, dyslipidemias, metabolic syndrome, and impaired insulin response to exercise. The purpose of the study was to determine the effects of a single bout of aerobic exercise on fasting serum insulin and glucose concentrations following 1464 kJ (350 kcal) of exercise and to determine if this response was associated with serum lipid concentrations in overweight AA women. Premenopausal AA women (n = 11, mean ± SD, age = 32.5 ± 4.8 yr., BMI = 29.8 ± 4.8 kg·m-2, % fat = 35.6 ± 6.3, VO2peak = 21.5 ± 3.6 ml·kg-1·min-1, total cholesterol = 4.8 ± 0.6 mmol·L-1, triglycerides = 0.60 ± 0.2 mmol·L-1, HDLC = 3.3 ± 0.5 mg·dL-1) performed 1464 kJ (350 kcal) of treadmill exercise at 60%-70%VO2peak. Fasting plasma insulin and glucose concentrations were collected 24-h prior to, and immediately, 24-h, and 48 h following exercise. Fasting insulin concentration increased immediately following exercise (Baseline=77.1 ± 10.42 vs. Immediately=117.4 ± 15.28 μU·mL-1, 95%CI= 32.71, 47.89; P<0.05). The change in insulin concentration from 24-h pre- to 24-h post-exercise was correlated with BMI (r= 0.51), VO2peak (r= -0.47), and the change in lipoprotein lipase activity (r=0.37) (P<0.05 for all). In conclusion, in sedentary AA women, the insulin response immediately following exercise may be elevated, and is not suppressed below pre-exercise concentrations during the 48-h following exercise. The insulin response 24-h following exercise is modestly associated with markers of lipoprotein metabolism.

Ethyl EPA and ethyl DHA cause similar and differential changes in plasma lipid concentrations and lipid metabolism in subjects with low-grade chronic inflammation

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to similarly lower plasma TG concentrations but differentially regulate plasma LDL-C and HDL-C concentrations. The aim of this study was to evaluate the common and differential effects of these ω-3 fatty acids on plasma lipids and lipoproteins and to assess the metabolic mechanisms of the effects. In a randomized, double-blind, crossover study, we assessed the effect of 10-week supplementation with 3 g/d pure EPA and pure DHA (both as ethyl ester, ≥97% purity) on plasma lipid and lipoprotein concentrations and activities of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 older (>50 y) men and postmenopausal women with some characteristics of metabolic syndrome and low-grade chronic inflammation. Both EPA and DHA lowered plasma TG concentrations and increased LDL-C/apoB and HDL-C/apoA-I ratios, but only DHA increased LDL-C concentrations. The reductions in plasma TG were inversely associated with the changes in LPL activity after both EPA and DHA supplementation. EPA lowered CETP, while DHA lowered LCAT activity. EPA and DHA worked differently in men and women, with DHA increasing LPL activity and LDL-C concentrations in women, but not in men. EPA and DHA exerted similar effects on plasma TG, but differences were observed in LDL-C concentrations and activities of some enzymes involved in lipoprotein metabolism. It was also noted that EPA and DHA worked differently in men and women, supporting sex-specific variations in lipoprotein metabolism.

Whey Protein Combined with Low Dietary Fiber Improves Lipid Profile in Subjects with Abdominal Obesity: A Randomized, Controlled Trial

Abdominal obesity is associated with elevated postprandial triglycerides (TG), an independent risk factor for cardiovascular diseases. Previous studies show that whey protein (WP) and dietary fiber may separately reduce postprandial TG. However, few studies have investigated the long-term effects of WP and dietary fiber on postprandial TG. We aimed to investigate the separate and combined long-term effects of WP and dietary fiber from wheat bran on postprandial TG and markers of lipid metabolism in subjects with abdominal obesity. We conducted a 12-week, double-blind, randomized, controlled, parallel intervention study. In a 2 × 2 factorial design, 73 adults were randomized to receive 60 g/day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber wheat bran products (HiFi; 30 g dietary fiber/day) or low-fiber refined wheat products (LoFi; 10 g dietary fiber/day). A high-fat meal test was conducted before and after the intervention. Sixty-five subjects were included in the final analyses. There were no differences between intervention groups in postprandial TG assessed as incremental area under the curve (iAUC). WP-LoFi had reduced postprandial TG assessed as total area under the curve (tAUC) and reduced fasting TG compared with all other groups, and reduced fasting apolipoprotein B-48 compared with MD-LoFi. There were no changes in lipoprotein lipase activity. Total cholesterol and apolipoprotein B-100 were reduced after WP intake compared with MD. Total cholesterol was increased after HiFi intake compared with LoFi. In conclusion, intake of WP in combination with low-fiber cereal products for 12 weeks had beneficial effects on postprandial TG tAUC and fasting TG, but not on postprandial TG iAUC in subjects with abdominal obesity. Combining WP with high-fiber wheat bran products did not improve lipid profile.

Technology and Pregnancy

Technology and Pregnancy

Decreased Concentrations of the Lipoprotein Lipase Inhibitor Angiopoietin-Like Protein 4 and Increased Serum Triacylglycerol Are Associated With Increased Neonatal Fat Mass in Pregnant Women With Gestational Diabetes Mellitus

Angiopoietin-like protein 4 (ANGPTL4) is an extracellular inhibitor of lipoprotein lipase (LPL) activity. No studies have been done in pregnancy in which hypertriglyceridemia and tissue-specific changes in LPL activity are present. The objective of the study was to determine the relationship between neonatal fat mass (FM) and concentrations of ANGPTL4 and triacylglycerols (TAG) in maternal and cord serum of pregnant women with gestational diabetes mellitus (GDM) compared with controls. Maternal blood samples (control, n = 90, and GDM, n= 80) and umbilical cord blood were drawn before and after vaginal delivery, respectively. Control and GDM subjects were grouped separately into 3 subgroups, according to neonatal FM: 0-25th percentiles, 25th-75th percentiles, and 75th-100th percentiles. Glucose, insulin, TAG, nonesterified fatty acids (NEFAs), and ANGPTL4 were determined in maternal and neonatal serum. Age and pregestational body mass index did not differ between GDM and control women in any subgroups. Maternal serum of GDM pregnant women who delivered the newborn with the highest FM showed the highest concentrations of TAG and NEFAs and lowest concentration of ANGPTL4, despite glucose and insulin concentrations being independent of changes in neonatal FM. However, cord serum of neonates of GDM patients with the highest FM showed higher concentrations of insulin and lower concentrations of TAG than those with lower neonatal FM but no significant differences in NEFAs or ANGPTL4 concentrations. In well-controlled GDM pregnancies, decreased maternal ANGPTL4 concentrations and a gradient of TAG toward the fetus are related with higher neonatal FM. However, in GDM fetuses with the highest FM, the potential effect of ANGPTL4 inhibiting adipose tissue LPL activity could be overcome by their hyperinsulinemia.

Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise.

BackgroundMany of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects.MethodsUsing a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL).ResultsThe intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state.ConclusionsThese findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

Effect of titanium on lipoprotein lipase activity in vivo and in vitro

Summary Lipoprotein lipase (LPL) is a major lipolytic enzyme in the intravascular metabolism of postprandial triglyceride-rich lipoproteins. This enzyme is synthesized and secreted by tissues and transported to the capillary endothelial surface. Decreased activity of this enzyme is suggested to be involved in arterial sequestration of lipoproteins and thus in the progression of atherosclerosis. Titanium salts are widely used in industry, medicine, and pharmacy for tablet coating, pharmaceuticals and cosmetic products. In this study the effect of titanium on post-heparin LPL activity is reported in vivo and in vitro. Methods Groups of Male Wistar rats were administered (i.p) with an acute dose of 2.5 mg/kg titanium chloride for 10 days and a chronic dose of 0.75 mg/kg for 30 and/or 60 days. Blood samples were then collected for LPL assay. For in vitro study, plasma aliquots were incubated in the presence of up to 50 mM titanium and the enzyme activity was measured. Results Animals exposed to acute dose of titanium showed about 20% reduction in LPL activity, whereas 31% and 36% reductions were observed in animals chronically exposed for 30 and/or 60 days, respectively. Titanium in vitro also led to enzyme inhibition, so that a decrease of 28–53% was seen in the presence of 0.1–50 mM titanium. This inhibition by titanium was potentiated when citrate and/or bicarbonate was present. Conclusion Although the mechanism of titanium effect on LPL activity in vivo and in vitro demands more investigations, the inhibitory effect of titanium ion in vivo should be considered seriously in subjects exposed to this metal ion. Changes in LPL activity may affect whole body lipid metabolism, a condition favorable for development and progression of atherosclerosis.

Regulation of Lipoprotein Lipase by Fasting in Epididymal and Mesenteric Adipocytes of Rats

There are marked variations in the activity of lipoprotein lipase (LPL) among adipose depots. The aim of this study was to compare the mechanisms of 24 h of fasting on LPL regulation between epididymal (EPI) adipocytes and mesenteric (MES) adipocytes in rats. 1-Day fasting consistently decreased activities of heparin-releasable LPL, total extractable LPL and cellular LPL markedly in both EPI and MES fat pads. LPL activity in MES fat pads was relatively lower than in the EPI fat pads. Consistent with data on LPL activity, the levels of expression of LPL mRNA in both nutritional states were lower in MES than EPI adipose tissue and isolated adipocytes. The decreased LPL activity after 1 day of fasting in MES adipocytes was explained mainly by a 50% decrease in the relative abundance of LPL mRNA level and a parallel 50% decrease in relative rate of LPL synthesis. In contrast, fasting of 1 day in EPI adipocytes decreased total LPL activity by 47% but did not affect LPL mRNA level or relative rate of LPL synthesis. A decrease in overall protein synthesis contributed to the decreased LPL activity after 1 day fasting both in EPI and MES adipocytes. In MES adipocytes the decrease in LPL activity, LPL mRNA and LPL synthesis were comparable, but in EPI adipocytes the changes in LPL activity were substantially larger than the changes in LPL mRNA level and LPL synthesis. Therefore, fasting decreased fat cell size, LPL activity, LPL mRNA level and relative rate of LPL synthesis in rats, and these effects were more marked in the MES adipocytes. These results clearly demonstrate the regional variations in the metabolic response of adipose tissue and LPL functions to fasting.

Insulin regulation of lipoprotein lipase (LPL) activity and expression in gilthead sea bream ( Sparus aurata)

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism by virtue of its capacity to hydrolyze triglycerides circulating in the form of lipoprotein particles. Here we analyzed the fasting effects of LPL in gilthead sea bream ( Sparus aurata) and also present the first study in fish of the role of insulin as a potential modulator of both LPL activity and expression. Fasting for 2 weeks provoked a clear decrease in adipose tissue LPL activity, concomitant with lower levels of plasma insulin, while no effects were observed in red muscle. To elucidate the specific role of insulin, increases of plasma insulin were experimentally induced by arginine and insulin injections. However, arginine predominantly stimulated glucagon over insulin secretion in this fish species while LPL activity did not change significantly in adipose tissue. Instead, insulin administration induced an increase in adipose tissue LPL activity 3 h after the injection, whereas LPL activity in red muscle was not affected. Changes in LPL activity were accompanied by an increase in LPL mRNA levels in the adipose tissue of insulin-injected gilthead sea bream, although changes in LPL expression were delayed in time with respect to variations in LPL activity. Finally, LPL mRNA levels in red muscle were similar between control and insulin-injected gilthead sea bream, suggesting that insulin does not play a direct role in the regulation of LPL in this tissue. The current study shows that LPL activity is regulated by nutritional condition and underscores the importance of insulin as a modulator of LPL activity and expression in the adipose tissue of gilthead sea bream.

Glucose administration downregulates lipoprotein lipase activity in vivo: a study using repeated intravenous fat tolerance test

Lipoprotein lipase (LPL) is a key factor determining the clearance of triglycerides from the circulation. The enzyme activity is tissue-specifically regulated by insulin, but it is not clear yet how insulin regulates the total LPL activity in the circulation. To answer such question, we measured LPL activity using the intravenous fat tolerance test (IVFTT) that was carried out 1 h before as well as 2 h and 4 h after oral administration of glucose (75 g) in eleven healthy male volunteers. In control experiments, no glucose was given to the subjects. Glucose administration resulted in an expected increase in plasma glucose and insulin and in a suppression of non-esterified fatty acid concentration. The LPL activity assessed in IVFTT as a k(2) rate constant did not change in control experiments and decreased to 78 % and 73 % of baseline values 2 h and 4 h after glucose administration, respectively (p=0.01). Similarly, LPL activity measured in the plasma after intravenous injection of heparin at the end of the experiments was 16 % lower (p<0.05) after glucose administration. In conclusion, LPL activity is already downregulated in vivo 2 h after glucose administration. The results of our study indicate that repeated IVFTT is a promising approach for studying acute changes in LPL activity.

Influence of trauma on plasma elimination of exogenous fat and on lipoprotein lipase activity and mass

Trauma is followed by an increased plasma clearance and oxidation of exogenous fat but the underlying mechanism is not fully understood. To examine the influence of a surgical trauma on the plasma elimination of exogenous triglycerides (TG) and its relationship with lipoprotein lipase (LPL) activity and LPL mass. Nine patients underwent a hypertriglyceridaemic clamp and a lipolytic capacity test before and after open abdominal surgery. The infusion rate was adjusted to maintain a stable TG concentration of 4 mmol x l(-1) during 180 min. The lipolytic capacity was determined as the change in LPL activity and mass following a bolus dose of 100 IU x kg BW(-1) heparin sodium. Postoperatively, the plasma elimination rate of fat was 2.6 times higher (P<0.001). Infusion of lipids in the postoperative state was followed by a smaller rise in free fatty acids (P<0.05) in comparison with the preoperative situation. The postoperative basal fasting LPL activity was half of that in the preoperative state and the LPL activity rose almost two-fold during the clamp. The heparin-induced rises in LPL activity and LPL mass were similar (n.s.) before and after surgery. A moderate surgical trauma is accompanied by a greater than two-fold rise in plasma elimination rate of exogenous fat despite a lower basal LPL activity and a virtually unchanged LPL pattern during infusion of lipids. Our study demonstrates that although trauma may substantially enhance the fat elimination capacity a significant proportion of the infused fat is not utilized for metabolic purposes.

Regulation of Lipoprotein Lipase by Protein Kinase Cα in 3T3-F442A Adipocytes

Lipoprotein lipase (LPL) is an important enzyme in adipocyte and lipid metabolism with complex cellular regulation. Previous studies demonstrated an inhibition of LPL activity and synthesis following depletion of protein kinase C (PKC) isoforms with long term treatment of 3T3-F442A adipocytes with 12-O-tetradecanoylphorbol-13-acetate. To identify the specific PKC isoforms involved, we treated cells with antisense oligonucleotides that block expression of specific PKC isoforms. An antisense oligonucleotide to PKC alpha inhibited LPL activity by 78 +/- 8%, whereas antisense oligonucleotides directed against PKC delta or PKC epsilon had no effect on LPL activity. The change in LPL activity was maximal at 72 h and was accompanied by a decrease in LPL protein and LPL synthetic rate but no change in LPL mRNA, suggesting regulation at the level of translation. However, PKC depletion resulted in no change in the polysome profile, indicating that translation initiation was not affected. However, the addition of cytoplasmic extracts from adipocytes treated with 12-O-tetradecanoylphorbol-13-acetate or PKC alpha antisense oligomers inhibited LPL translation in vitro. This inhibition of LPL translation in vitro was lost when the LPL mRNA transcript did not contain nucleotides 1599-3200, thus implicating the 3'-untranslated region of LPL in the regulation of translation by PKC depletion. Both LPL activity and Raf1 activity were decreased in parallel following depletion of either total PKC or specific inhibition of PKC alpha. An antisense oligonucleotide to RAF1, which inhibited RAF1 activity, also inhibited LPL activity by 48 +/- 10%, and this decrease in LPL activity was not accompanied by a change in LPL mRNA. Cells were treated with U0126, a specific inhibitor of the ERK-activating kinases MEK1 and MEK2. Although U0126 inhibited ERK1 and ERK2 phosphorylation, U0126 had no effect on LPL activity, indicating that MEK/ERK pathways were not involved in this mechanism of LPL regulation. Together, these data indicate that PKC alpha and RAF1 are important in the translational regulation of LPL in adipocytes and that the mechanism of regulation is probably through an ERK-independent pathway.

Changes in LPLa and reverse cholesterol transport variables during 24-h postexercise period

We investigated the time course of exercise-induced lipoprotein lipase activity (LPLa) and reverse cholesterol transport (RCT) during the 24-h postexercise period. Subjects were 10 sedentary normolipidemic males [NTG; fasting triglyceride (TG) = 89.1 +/- 8.6 mg/dl] and 6 hyperlipidemic males (HTG; fasting TG = 296.8 +/- 64.0 mg/dl). Each subject performed a control trial (no exercise) and 4 exercise trials. In the exercise trials, a subject jogged on a treadmill at 60% of his maximal O(2) consumption for 1 h. Pre- and postheparin blood samples were taken before exercise (baseline) and at 4, 8, 12, and 24 h after exercise. There was no group difference in LPLa (P > 0.05) over the time points. When the LPLa data from the two groups were combined, LPLa at 24 h after exercise was higher than baseline or at 4, 8, 12 h after exercise (P < 0.05). Plasma TG and lecithin-cholesterol acyltransferase activity (LCATa) were higher in HTG than in NTG, and the total high-density lipoprotein-cholesterol (HDL(tot)-Chol) was lower in HTG than in NTG (P < 0.05). HDL(2)-Chol, LCATa, and cholesterol ester transfer protein activity did not differ during the 24-h postexercise period (P > 0.05). These results suggest that LPLa is still increasing 24 h after an acute aerobic exercise and that the magnitude of the increase in exercise-induced LPLa in HTG was similar to that in NTG. Furthermore, in the sedentary population with or without HTG, the variables related to RCT do not change during the 24-h period after exercise.

Time course of changes in lipoprotein lipase activity in rat skeletal muscles during denervation-reinnervation.

The effects of denervation-reinnervation after sciatic nerve crush on the activity of extracellular and intracellular lipoprotein lipase (LPL) were examined in the soleus and red portion of gastrocnemius muscles. The activity of both LPL fractions was decreased in the two muscles within 24 h after the nerve crush and remained reduced for up to 2 wk. During the reinnervation period, LPL activity was still reduced in the soleus and started to increase only on the 40th day. In the red gastrocnemius, LPL activity increased progressively with reinnervation, exceeding control values on the 30th day post-crush. The LPL activity in the soleus from the contralateral to denervated hindlimb was also affected, being increased on the postoperation day and then gradually decreased during the following days. In conclusion, the time course of changes in muscle LPL activity after nerve crush confirmed the predominant role of nerve conduction in controlling muscle potential to take up free fatty acids derived from the plasma triacylglycerols. However, other factors, such as muscle fiber composition and the fiber transformation, should also be considered in this aspect of the denervation-reinnervation process. Moreover, it was found that denervation of muscles from one hindlimb may influence LPL activity in muscles from the contralateral leg.

Responses of adipose tissue lipoprotein lipase to weight loss affect lipid levels and weight regain in women.

This study determines whether changes in abdominal (ABD) and gluteal (GLT) adipose tissue lipoprotein lipase (LPL) activity in response to a 6-mo weight loss intervention, comprised of a hypocaloric diet and low-intensity walking, affect changes in body composition, fat distribution, lipid metabolism, and the magnitude of weight regain in 36 obese postmenopausal women. Average adipose tissue LPL activity did not change with an average 5.6-kg weight loss, but changes in LPL activity were inversely related to baseline LPL activity (ABD: r = -0.60, GLT: r = -0.48; P < 0.01). The loss of abdominal body fat and decreases in total and low-density lipoprotein cholesterol were greater in women whose adipose tissue LPL activity decreased with weight loss despite a similar loss of total body weight and fat mass. Moreover, weight regain after a 6-mo follow-up was less in women whose adipose tissue LPL activity decreased than in women whose LPL increased (ABD: 0.9 +/- 0.5 vs. 2.8 +/- 0.6 kg, P < 0.05; GLT: 0.2 +/- 0.5 vs. 2.8 +/- 0.5 kg, P < 0.01). These results suggest that a reduction in adipose tissue LPL activity with weight loss is associated with improvements in lipid metabolic risk factors with weight loss and with diminished weight regain in postmenopausal women.

Lipid metabolism in the fetus and the newborn.

During late gestation, although maternal adipose tissue lipolytic activity becomes enhanced, lipolytic products cross the placenta with difficulty. Under fasting conditions, free fatty acids (FFA) are used for ketogenesis by the mother, and ketone bodies are used as fuels and lipogenic substrates by the fetus. Maternal glycerol is preferentially used for glucose synthesis, saving other gluconeogenic substrates, like amino acids, for fetal growth. Placental transfer of triglycerides is null, but essential fatty acids derived from maternal diet, which are transported as triglycerides in lipoproteins, become available to the fetus owing to the presence of both lipoprotein receptors and lipase activities in the placenta. Diabetes in pregnancy promotes lipid transfer to the fetus by increasing the maternal-fetal gradient, which may contribute to an increase in body fat mass in newborns of diabetic women. Deposition of fat stores in the fetus is very low in the rat but high in humans, where body fat accretion occurs essentially during the last trimester of intra-uterine life. This is sustained by the intense placental transfer of glucose and by its use as a lipogenic substrate, as well as by the placental transfer of fatty acids and to their low oxidation activity. During the perinatal period an active ketonemia develops, which is maintained in the suckling newborn by several factors: (i) the high-fat and low-carbohydrate content in milk, (ii) the enhanced lipolytic activity occurring during the first few hours of life, and (iii) both the uptake of circulating triglycerides by the liver due to the induction of lipoprotein lipase (LPL) activity in this organ, and the presence of ketogenic activity in the intestinal mucose. Changes in LPL activity, lipogenesis and lipolysis contribute to the sequential steps of adipocyte hyperplasia and hypertrophia occurring during the extra-uterine white adipose tissue development in rat, and this may be used as a model to extrapolate the intra-uterine adipose tissue development in other species, including humans.

Lipid metabolism in the fetus and the newborn

During late gestation, although maternal adipose tissue lipolytic activity becomes enhanced, lipolytic products cross the placenta with difficulty. Under fasting conditions, free fatty acids (FFA) are used for ketogenesis by the mother, and ketone bodies are used as fuels and lipogenic substrates by the fetus. Maternal glycerol is preferentially used for glucose synthesis, saving other gluconeogenic substrates, like amino acids, for fetal growth. Placental transfer of triglycerides is null, but essential fatty acids derived from maternal diet, which are transported as triglycerides in lipoproteins, become available to the fetus owing to the presence of both lipoprotein receptors and lipase activities in the placenta. Diabetes in pregnancy promotes lipid transfer to the fetus by increasing the maternal-fetal gradient, which may contribute to an increase in body fat mass in newborns of diabetic women. Deposition of fat stores in the fetus is very low in the rat but high in humans, where body fat accretion occurs essentially during the last trimester of intra-uterine life. This is sustained by the intense placental transfer of glucose and by its use as a lipogenic substrate, as well as by the placental transfer of fatty acids and to their low oxidation activity. During the perinatal period an active ketonemia develops, which is maintained in the suckling newborn by several factors: (i) the high-fat and low-carbohydrate content in milk, (ii) the enhanced lipolytic activity occurring during the first few hours of life, and (iii) both the uptake of circulating triglycerides by the liver due to the induction of lipoprotein lipase (LPL) activity in this organ, and the presence of ketogenic activity in the intestinal mucose. Changes in LPL activity, lipogenesis and lipolysis contribute to the sequential steps of adipocyte hyperplasia and hypertrophia occurring during the extra-uterine white adipose tissue development in rat, and this may be used as a model to extrapolate the intra-uterine adipose tissue development in other species, including humans.

SYNERGISM BETWEEN LIPOPOLYSACCHARIDE AND INTERFERON γ IN THE REGULATION OF LIPOPROTEIN LIPASE IN MACROPHAGES

The regulation of macrophage lipoprotein lipase (LPL) by cytokines is potentially of crucial importance in the pathogenesis of atherosclerosis and in septic shock. The effect of combinations of lipopolysaccharide (LPS) and cytokines on the expression of LPL in macrophages was studied using the murine J774.2 cell line. The suppression of heparin-releasable LPL activity produced by combinations of LPS and interleukin 1 (IL-1), IL-11 or tumour necrosis factor α(TNF-α) was substantially less than that expected from the simple additive action of the corresponding two effectors. By contrast, co-exposure of the cells to LPS and interferon γ(IFN-γ) resulted in a more than additive, synergistic, suppression of LPL activity which was, additionally, also observed when the rat alveolar macrophage NR8383 cell line was studied. This synergistic action was also observed when J774.2 macrophages were exposed initially to IFN-γ (priming), washed and then treated with LPS. A comparison of the LPL activity and mRNA levels produced by the synergistic action of LPS and IFN-γand the priming action of IFN-γ indicated that a combination of mRNA metabolism (transcription or RNA stability), translation and post-translational mechanisms were responsible for the observed changes in LPL activity. These data, therefore, suggest that combinations of LPS and cytokines may be more important than the presence or absence of any given single effector in the modulation of LPL function during infection.

Hepatic microsomal triglyceride transfer protein gene expression in carbohydrate-induced hypertriglyceridemia

The microsomal triglyceride transfer protein (MTP) facilitates the assembly of very low density lipoproteins (VLDL). To investigate the effects of carbohydrate (CHO)-induced hypertriglyceridemia (HTG) on the hepatic expression of the MTP gene, Golden Syrian hamsters were fed fructose (FR) and sucrose (SUC) enriched diets. Changes in fasting plasma glucose (FPG), insulin, free fatty acids (FFA), TG, VLDL-TG and VLDL-protein were determined. Abundance of hepatic MTP-mRNA was compared to those of albumin (ALB)-mRNA and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)-mRNA. Hepatic secretion rates (SR) of VLDL-TG and VLDL-PR were assessed after intravenous Triton WR-1339 injection. Lipoprotein lipase (LpL) activity of the epididymal fat pads was determined. As compared to the control and SUC, FR increased plasma insulin (FR = 238+24, SUC = 115±17, control = 82±16 μU/ml, p < 0.0001), FFA (FR = 1.93±0.24, SUC = 1.35±0.1, control = 1.47±0.13 mEq/L, p < 0.03) and TG (FR = 215±47, SUC = 93±7, control = 71±16 mg/dl, p < 0.01), without affecting FPG. There was no change in LpL activity. Fructose-feeding increased VLDL-TG-SR (FR = 2.95±0.26, SUC = 1.28±0.34, control = 2.18±0.26 mg/kg.wt/h −1, p < 0.004), but not VLDL-protein-SR. MTP-mRNA abundance did not change when compared to albumin mRNA, however FR-fed hamsters had lower MTP mRNA abundance when compared to GAPDH mRNA (FR = 0.96±0.13, SUC = 1.15±0.14, control = 1.49±0.14 MTP GAPDH-mRNA, p < 0.05). The finding that FR-feeding increased VLDL-TG secretion without any increase in MTP mRNA proves that CHO-induced HTG can occur without an increase in hepatic MTP gene expression.

Short-term effects of leptin on lipid metabolism in the rat

In this study, we have examined the short-term effects of leptin on lipid metabolism in the rat. Acute leptin administration induced hypertriglyceridaemia (31% increase in plasma triacylglycerols) which was not associated with changes in lipoprotein lipase activity in white adipose tissue. Surprisingly, leptin administration did not induce any changes in the lipogenic rate in either white adipose tissue or liver. Leptin administration caused a decreased tissue uptake of exogenous 14C-triacylglycerols. These data suggest that leptin induces important changes in lipid uptake in adipose tissue and skeletal muscle which could be responsible for the observed hypertriglyceridaemia.