Lipoprotein Lipase Activity In Liver Research Articles

Embryo thermal manipulation modifies development and hepatic lipid metabolism in post-hatch layer-type chicks.

Incubation temperature is a crucial environmental factor affecting embryonic development and chick quality. Metabolism during the embryonic stage, particularly liver lipid metabolism, is essential for the growth and development of poultry. This study aimed to investigate the effects of embryo thermal manipulation with high (TMH, 39.5 °C, 65% RH, 8h/d) and low (TML, 20 °C, 65% RH, 1h/d) temperatures during 8th to 15th embryonic age on hatching performance and liver lipid metabolism in layer chicks. Additionally, the duration of TM effects was evaluated through a short-term feeding trial. The results indicated that TMH accelerated the hatching process without significantly affecting hatchability and growth performance. In contrast, TML delayed hatching time and significantly reduced hatchability and chick quality. After hatching, TML also increased residual yolk weight and reduced the relative liver weight in relation to body weight and yolk-free body mass. Moreover, lipid droplets in the liver were stained with Oil Red O, and the lipid content in the liver and serum was further detected. TMH had no significant impact on triglyceride (TG) and total-cholesterol (TCHO) content in the liver and serum but upregulated the expression of lipogenesis-related genes ACC, Fas, and Fatp1 compared to the TML group. Conversely, TML significantly reduced liver TG content, enhanced lipoprotein lipase (LPL) activity, and promoted the expression of lipid oxidation-related genes CPT-1, PGC-1α, and PPARα. At 7 d of age, liver LPL activity was significantly increased in the TMH group. However, there were no significant changes in the content of TG and TCHO in the liver and the expression of lipid metabolism-related genes in the TML group. Overall, these results indicate that embryonic TM alters hatching performance and liver lipid metabolism in layer chicks. TML reduces TG content by increasing liver lipid oxidation capacity. However, this effect is not long-lasting, as the influence of TM diminishes as the chicks develop.

Effects of dietary supplementation with green tea waste on growth, digestive enzyme and lipid metabolism of juvenile hybrid tilapia, Oreochromis niloticus×O. aureus.

An 8-week feeding trial was conducted to evaluate the effects of dietary supplementation with green tea waste (GTW) on growth, digestive enzyme and lipid metabolism of juvenile hybrid tilapia, Oreochromis niloticus×O. aureus. The fish (initial mean body weight, 12.63±0.75g) were fed five experimental diets that included 0 (control), 0.8, 1.6, 3.2 or 6.4% of GTW in triplicate aquaria, twice daily. Growth performance, plasma metabolites content and liver and intestine digestive enzyme activities were determined. Fish accepted well all experimental diets during the trial, and no mortality was observed. The weight gain increased (P<0.05) with the increase in GTW inclusion level up to 1.6%, after which it decreased, but no significant differences between the control and high level (3.2 or 6.4% of GTW) groups were observed. Moreover, fish fed on diets containing 0.8 and 1.6% GTW had lower feed conversion ratio (FCR, 1.75 and 1.73, respectively) and had better protein deposition (higher protein efficiency ratio, PER, 1.73 and 1.71, respectively), compared to other treatments. No differences among groups were observed in whole body and dorsal muscle composition with the exception of lipid content which was lower in fish fed 6.4% GTW diets, compared to other treatments. Lipase activities in liver or intestine were higher in fish fed GTW-supplemented diets with the exception of intestine lipase activities, which was unaffected, compared to the control. Similarly, liver lipoprotein lipase activities were also increased in fish fed diets supplemented a medium dose of GTW (1.6 or 3.2%), compared to other treatments. However, intestine amylase activities were decreased in fish fed diets containing a high dose of GTW (3.2 and 6.4%); while the liver amylase activities were unaffected by the GTW supplementation. Blood chemistry parameters were affected by GTW inclusion, except the values of triglycerides, which was unaffected. The values of total cholesterol, HDL cholesterol and LDL cholesterol increased with increasing GTW inclusion level up to 3.2%, after which the values decreased. These results indicate that diets supplemented with appropriate concentration of GTW (from 0.8 to 1.6%) may potentially serve as an effective functional food and additive for tilapia to improve growth performance, digestion efficacy and fat metabolism.

Changes in activities and mRNA expression of lipoprotein lipase and fatty acid synthetase in large yellow croaker,Larimichthys crocea(Richardson), during fasting

Over-winter fasting and man-made food deprivation to increase meat quality are common in the process of large yellow croaker (Larimichthys crocea) aquaculture. This study aimed to determine the changes in lipoprotein lipase (LPL) and fatty acid synthetase (FAS) activities and mRNA expressions, and the relationships between these changes and fat content in large yellow croaker liver and muscle tissues during fasting. A total of 2933 bp LPL cDNA, including an open reading frame of 1533 bp encoding 510 amino acids, and a 1233 bp fragment of FAS cDNA coding 411 amino acids were cloned. Expressions of both genes were ubiquitous. During a 35-day fasting period, the hepatosomatic index and fat content in muscle and liver were significantly decreased (P < 0.05). mRNA levels of LPL increased significantly during the fasting period except the first 3 days, and FAS mRNA levels decreased significantly in both muscle and liver (P < 0.05) although there were some fluctuations. Muscle and liver LPL activities were significantly higher following fasting for 7 days, decreased to the initial value following fasting for 14 days, and elevating significantly afterwards (P < 0.05). FAS activities in muscle and liver maintained a significantly decreasing trend during the short-term fasting (P < 0.05) and kept obviously rising thereafter (P < 0.05). Activities and mRNA levels of both LPL and FAS were not always consistent, which implied that both pre-translational and post-translational regulations existed during fasting. Our results suggest that the reasonable fasting time is 21 days before harvesting when fat content decreased significantly.

Fish oil diet in pregnancy and lactation reduces pup weight and modifies newborn hepatic metabolic adaptations in rats.

To determine the effects of a diet containing fish oil (FD) during pregnancy and lactation in rats on the metabolic adaptations made by the offspring during early extrauterine life and to compare it to an olive oil diet (OD). Rats were mated and randomly allocated to OD or FD containing 10% of the corresponding oil. During lactation, litters were adjusted to eight pups per dam. Fetuses of 20days and pups of 0, 1, 10, 20 and 30days of age were studied. Body weight and length were lower in pups of the FD group from birth. The diet, milk, pups' plasma and liver of FD group had higher proportions of n-3 LCPUFA, but the content of arachidonic acid (ARA) was lower. Plasma glucose was higher, but unesterified fatty acids, triacylglycerols (TAG), 3-hydroxybutyrate and liver TAG in 1-day-old pups were lower in the FD group, and differences in some of these variables were also found in pups up to 30days old. Liver lipoprotein lipase activity and mRNA expression, and the expression of carnitine palmitoyl transferase I, acyl-CoA oxidase and 3-hydroxy 3-methyl glutaryl-CoA synthase increased more at birth in pups of the FD group, but the expression of sterol regulatory element binding protein-1c and Δ6-desaturase mRNA was lower in the FD group. Maternal intake of high n-3 LCPUFA retards postnatal development, which could be the result of impaired ARA synthesis, and affects hepatic metabolic adaptations to extrauterine life.

Effects of dietary choline supplementation on growth performance, lipid deposition and intestinal enzyme activities of blunt snout breamMegalobrama amblycephalfed high-lipid diet

This study aimed to investigate the effects of dietary choline supplementation on growth, lipid deposition and intestinal enzyme activities of Megalobrama amblycephala. Fish were fed four diets with two lipid levels (50 and 150 g kg−1) and two choline supplementations (600 and 1600 mg kg−1) for 8 weeks. Feed conversion ratio (FCR), viscerosomatic index (VSI), hepatosomatic index (HSI), intraperitoneal fat (IPF) ratio, whole-body and muscle lipid contents, intestinal lipase activities and lipoprotein lipase (LPL) activities all increased significantly (P < 0.05) as lipid levels increased, whereas the opposite was true for whole-body and muscle moisture contents and intestinal amylase activities. VSI, IPF ratio and whole-body lipid contents all decreased significantly (P < 0.05) with increasing dietary choline supplementations. Weight gain, muscle moisture content all increased significantly (P < 0.05) with increasing dietary choline supplementations when dietary lipid levels reached 150 g kg−1, whereas the opposite was true for FCR, IPF ratio, IPF and liver LPL activities. In addition, abnormal hepatocytes were found in the liver of fish fed 150 g kg−1 lipid with 600 mg kg−1 choline supplementation. The result of this study indicated that extra choline supplementation can improve growth performance, intestinal enzymes activities and reduce excessive lipid deposition of M. amblycephala fed high lipid.

Hypolipidemic effect of proteoglycans isolated from sweet potato (Ipomoea batatas LAM) in hyperlipidemia rats

Effects of sweet potato proteoglycans (SPG) in rats fed high lipid diets were investigated. Serum lipid indices for SPG were evaluated. SPG had hypolipidemic effects that were correlated with dosage. There were no significant (p>0.05) differences in hypolipidemic effects between SPG varieties of different molecular weights. SPG-1 (Mw value: 508.3 kDa) significantly (p<0.05) reduced serum total cholesterol (TC), triacylglyceride (TAG), low density lipoprotein cholesterol (LDL-C), and apolipoprotein (Apo) B levels, and the arteriosclerosis index (AI), and induced serum high density lipoprotein cholesterol (HDL-C), ApoA-I, lecithin cholesterol acyltransferase (LCAT), and liver lipoprotein lipase (LPL) activities, compared with controls. The whole blood viscosity and red blood cell (RBC) membrane microviscosity were also decreased. Hypolipidemic effects were mediated via elevation of the serum HDL-C concentration by induction of LACT activity, an increased ApoA-I concentration, and a reduction in the serum lipid concentration due to regulation of LPL activity.

The hypolipidemic activity of chitosan nanopowder prepared by ultrafine milling

The hypolipidemic activities of high and low molecular weights of chitosan nanopowders (HMW-chitosan-NP: 315kDa; LMW-chitosan-NP: 51kDa) prepared by ultrafine milling were evaluated in rats. The results showed that the hypolipidemic activity of chitosan nanopowder was better than ordinary chitosan, and LMW-chitosan-NP was superior to HMW-chitosan-NP in hypolipidimic activity. Compared with ordinary chitosan, chitosan nanopowder increased the fecal lipids and the activities of serum and liver lipoprotein lipase (LPL) and hepatic lipase (HL) of rats. Rats receiving LMW-chitosan-NP excreted less lipids in feces, but showed higher serum and liver LPL and HL activities compared with those fed HMW-chitosan-NP. These results suggested that compared with ordinary chitosan, the increased hypolipidemic activity of chitosan nanopowder might be attributed to its ability on increasing fecal lipid excretions and stimulating LPL and HL activities, and the better stimulation of LMW-chitosan-NP in activities of these lipases might help it to exceed HMW-chitosan-NP in hypolipidemic activity.

A comparative study on hypolipidemic activities of high and low molecular weight chitosan in rats

The hypolipidemic activities of high (712.6kDa) and low (39.8kDa) molecular weight chitosan (HMWC and LMWC) were evaluated in rats fed high-fat diets. Thirty-two male Sprague-Dawley rats in four groups were fed on three high-fat diets with each of them containing HMWC, LMWC or cellulose (high-fat control), and a control normal-fat diet for eight weeks. Compared with HMWC group, LMWC group showed decreased body weight gain, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), as well as decreased liver triglyceride (TG). Fecal fat and cholesterol of LMWC group was lower than those of HMWC group. However, the activities of liver and serum lipoprotein lipase (LPL) of LMWC group were increased compared with HMWC group. The obtained results suggested that hypolipidemic activity of LMWC was better than HMWC, which might be partially attributed to the increase of serum and liver LPL activities.

Crocetin improves the insulin resistance induced by high-fat diet in rats.

The amelioration of insulin resistance by treatment with crocetin is closely related to the hypolipidaemic effect. The present study is designed to clarify the insulin-sensitizing mechanism of crocetin by elucidating the mechanism of regulation of lipid metabolism by crocetin. Rats given a high-fat diet were treated with crocetin for 6 weeks before hyperinsulinaemic-euglycaemic clamp. 14C-palmitate was used as tracer to track the fate of non-esterified fatty acids or as substrate to measure beta-oxidation rate. Triglyceride clearance in plasma and lipoprotein lipase activity in tissues were tested. Content of lipids in plasma and tissues was determined. Real-time PCR was used to assay the level of mRNA from genes involved in non-esterified fatty acid and triglyceride uptake and oxidation. Crocetin prevented high-fat-diet induced insulin resistance (increased clamp glucose infusion rate), raised hepatic non-esterified fatty acid uptake and oxidation, accelerated triglyceride clearance in plasma, enhanced lipoprotein lipase activity in liver, and reduced the accumulation of detrimental lipids (DAG and long-chain acyl CoA) in liver and muscle. Genes involved in hepatic lipid metabolism which are regulated by peroxisome proliferator-activated receptor-alpha, were modulated to accelerate lipid uptake and oxidation. Through regulating genes involved in lipid metabolism, crocetin accelerated hepatic uptake and oxidation of non-esterified fatty acid and triglyceride, and reduced lipid availability to muscle, thus decreasing lipid accumulation in muscle and liver, and consequently improving sensitivity to insulin.

Relationship between lipoprotein lipase and peroxisome proliferator-activated receptor-α expression in rat liver during development

The present study was addressed to determine whether the high expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in rat liver during the perinatal stage plays a role in the induction of liver lipoprotein lipase (LPL) expression and activity. Parallel increases in liver mRNA PPAR-alpha and LPL activity were found in newborn rats, and after a slight decline, values remained elevated until weaning. Anticipated weaning for 3 days caused a decline in those two variables as well as in the mRNA LPL level, and a similar change was also found in liver triacylglycerol concentration. Force-feeding with Intralipid in 10-day-old rats or animals kept fasted for 5 h showed high mRNA-PPARalpha and -LPL levels as well as LPL activity with low plasma insulin and high FFA levels, whereas glucose and a combination of glucose and Intralipid produced low mRNA-PPARalpha and -LPL levels as well as LPL activity. Under these latter conditions, plasma insulin and FFA levels were high in those rats receiving the combination of glucose and Intralipid, whereas plasma FFA levels were low in those force-fed with glucose. It is proposed that the hormonal and nutritional induction of liver PPAR-alpha expression around birth and its maintained elevated level throughout suckling is responsible for the induction of liver LPL-expression and activity during suckling.

Isoproterenol increases active lipoprotein lipase in adipocyte medium and in rat plasma

White adipose tissue (WAT) lipoprotein lipase (LPL) activity channels diet fat towards storage in adipocytes. Adrenaline (ADR) is accepted to reduce WAT or adipocyte LPL activity (LPLa), but available data are not clear-cut regarding long exposure to ADR in vitro or in vivo. We studied the effects of long exposures to ADR or β-adrenergic agonist on LPL: in isolated rat adipocytes (3 h) and in rats (>1 day). Isoproterenol (ISO) (1 μM) did not alter LPLmRNA nor LPLa in adipocytes, but increased LPLa in medium more than twofold (3.58 ± 0.35 vs. 1.32 ± 0.35 mU/10 6 adipocytes, P < 0.001). Effect was time (not present at 1 h, clear at 2 h) and concentration dependent (high sensitivity from 10 to 100 nM, max at 1 μM). Adenylate cyclase activator or cyclic AMP (cAMP) analogue produced a similar increase. Thus in adipocytes ISO produced an increase in LPLa release and/or a decrease in extracellular LPLa degradation. ADR or ISO treated rats had a two to fourfold decrease in WAT LPLa vs. unchanged LPLmRNA. This decrease was 10-fold in WAT heparin-releasable LPLa (5.7 ± 0.6 vs. 57.3 ± 10.2 mU/g, P < 0.001), which represents peri/extracellular LPLa. Plasma LPLa was increased 11-fold by ADR (3.30 ± 0.58 vs. 0.32 ± 0.08 mU/ml, P < 0.001) whereas only threefold by ISO ( P > 0.01). We suggest that in vivo ADR increased release of active LPL to plasma from endothelial cells of LPL-rich tissue(s)—WAT was probably one of these tissues releasing LPL since it lost 90% of its peri/extracellular LPLa—and/or decreased degradation of plasma active LPL. Since liver LPLa was not increased, plasma active LPL might be kept away from hepatic degradation by binding to stabilising entities in plasma (fatty acids (FA), lipoproteins or soluble heparan sulphates (HS)). In conclusion, we believe this is the first report stating that: (a) ISO increases LPLa in isolated adipocyte medium, and (b) ADR administration to rats decreases WAT extracellular active LPL and increases preheparin plasma active LPL.

Regulation of Lipoprotein Lipase by the Oxysterol Receptors, LXRα and LXRβ

Lipoprotein lipase (LPL) is a key enzyme for lipoprotein metabolism and is responsible for hydrolysis of triglycerides in circulating lipoproteins, releasing free fatty acids to peripheral tissues. In liver, LPL is also believed to promote uptake of high density lipoprotein (HDL)-cholesterol and thereby facilitate reverse cholesterol transport. In this study we show that the Lpl gene is a direct target of the oxysterol liver X receptor, LXRalpha. Mice fed diets containing high cholesterol or an LXR-selective agonist exhibited a significant increase in LPL expression in the liver and macrophages, but not in other tissues (e.g. adipose and muscle). Studies in Lxr-deficient mice confirmed that this response was dependent more on the presence of LXRalpha than LXRbeta. Analysis of the Lpl gene revealed the presence of a functional DR4 LXR response element in the intronic region between exons 1 and 2. This response element directly binds rexinoid receptor (RXR)/LXR heterodimers and is sufficient for rexinoid- and LXR agonist-induced transcription of the Lpl gene. Together, these studies further distinguish the roles of LXRalpha and beta and support a growing body of evidence that LXRs function as key regulators of lipid metabolism and are anti-atherogenic.

A High Glycemic Index Starch Diet Affects Lipid Storage–Related Enzymes in Normal and to a Lesser Extent in Diabetic Rats

The of this study was to evaluate the chronic effects of a high (waxy corn) vs. a low (mung beans) glycemic index starch diet on the lipogenic enzymes, fatty acid synthase (FAS) and lipoprotein lipase (LPL). Normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats consumed a diet containing 575 g/kg carbohydrates either as waxy cornstarch (WCS) or as mung bean starch (MBS). After 3 wk, neither body weights nor relative epididymal fat pad weights differed. In diabetic rats, the WCS diet induced high basal plasma insulin levels. Plasma triglycerides were not significantly affected by diet in either normal or diabetic rats. Adipose tissue and liver LPL activities were not modified by the type of starch in the diet. In normal rats, FAS activity and gene expression in epididymal adipose tissue but not in liver were greater in rats consuming the WCS diet than in those consuming MBS. To evaluate the implication of insulin in this regulation, two genes regulated by insulin [GLUT4 and phosphoenolpyruvate carboxykinase (PEPCK)] were also studied. The high glycemic index WCS diet compared with the low glycemic index MBS diet resulted in lower hepatic PEPCK mRNA in both normal and diabetic rats. Normal, but not diabetic rats fed WCS had greater GLUT4 gene expression in adipocytes than did those fed MBS. We conclude that the total replacement of 575 g/kg low glycemic index starch by a high glycemic index starch for 3 wk caused the following in normal rats: 1) high FAS activity and mRNA in adipose tissue but not in liver and 2) high GLUT4 gene expression in adipose tissue. In both normal and diabetic rats this same diet resulted in lower hepatic PEPCK mRNA. Therefore, high glycemic index starch diet is implicated in stimulating FAS activity and lipogenesis and might have undesirable long-term metabolic effects.

Hormonal regulation of lipoprotein lipase activity from 5-day-old rat hepatocytes

Lipoprotein lipase (LPL) activity is known to be synthesized, active and functional in the 1-day-old rat liver: it peaks just at birth triggered by parturition. During suckling LPL mRNA, LPL synthesis and LPL activity are still high at 5 days and then fade reaching adult values at weaning. How LPL expression is gradually extinguished is not known. Therefore we studied the effect of different doses of several hormones on LPL activity released by incubated hepatocytes from 5-day-old rats. In the presence of heparin the release of LPL activity in the medium was linear until 3 h and was always significantly increased vs. without heparin. At 3 h in the presence of heparin the main hormonal effects were: dose-independent increase (30–60%) with dexamethasone; dose-dependent increase (20–60%) with glucagon; dose-independent decrease (50–60%) with ethinylestradiol, testosterone, progesterone and prolactin; no effect with insulin; 20–40% increase with adrenaline <1 mM but 40–50% decrease with noradrenaline <10 μM. Increase of LPL release by glucagon and adrenaline agrees with the increased LPL expression we previously found in an undifferentiated hepatoma cell line when the adenylate cyclase/protein kinase A pathway was activated. The effect of glucagon is concordant with our previous observations that fasting increases liver LPL activity in neonatal rats. The high estradiol levels known to be present in male and female 9–19-day-old rats might contribute to liver LPL extinction during suckling.

Effect of starvation on lipoprotein lipase activity in the liver of developing rats

Liver lipoprotein lipase activity in neonatal (1- and 5-day-old) rats was 2–3-times that in the liver of adult rats. In mid-suckling (15-day-old) or weaned (30-day-old) animals, it was not significantly different from the low activity detected in adult rats. Starvation resulted in a 3-fold increase of lipoprotein lipase activity in the neonatal liver, but did not affect the activity in the liver of mid-suckling, weaned or adult rats. When isolated livers from both 1- and 5-day-old pups were perfused with heparin, a sharp peak of lipoprotein lipase activity appeared in the perfusate. In fed neonates, the peak area accounted for about 70% of the total (released + non-releasable) activity. In starved neonates, the proportion of heparin-releasable activity increased up to about 90%. These results indicate that neonatal rat liver lipoprotein lipase activity is markedly affected by changes in the nutritional status of the animal, and the effect is restricted to the vascular pool of the enzyme, as was reported in extrahepatic tissues from adult rats.

Regulation of lipoprotein lipase activity in the sand rat: Effect of nutritional state and cAMP modulation

The sand rat ( Psammomys obesus) is a desert rodent in which obesity and diabetes mellitus appeared only subsequent to feeding laboratory animal chow. To study the role of lipoprotein lipase in the development and maintenance of obesity in the sand rat, enzyme activity in various organs and in plasma of sand rats or albino rats was determined following a 20-hour fast, or 16 hours after injection of cholera toxin. Despite comparable change in body weight, an altered pattern of enzyme distribution and regulation was observed in the sand rat. Neither fasting nor cholera toxin had an effect on heart and daiphragm muscle lipoprotein lipase activity of the sand rat, but caused a 1.5- to 2-fold increase in the treated albino rats. By using an isolated perfused heart system, we were able to measure enzyme activity present in the heparin-releasable fraction that represents the functional pool of the enzyme. In both species, the heparin-releasable fraction of the heart increased twofold following fasting, though initial values were lower in sand rat. In both species, fasting and cholera toxin administration resulted in an increase in plasma and liver lipoprotein lipase activity. Adipose tissue lipoprotein lipase activity of sand rat, unlike the albino rats, was similar in the various fat regions and was not lowered by food deprivation or cholera toxin administration. After both treatments, sand rat plasma insulin levels exceeded fivefold those of albino rats. Adipose tissue lipoprotein lipase activity of fed and fasted normal and diabetic sand rats correlated negatively with plasma insulin and glucose levels. It is concluded that redistribution of heart lipoprotein lipase activity toward its functional pool in the fasting state is an important response of the enzyme to nutritional stimuli and may occur with or without increase in the residual enzymic activity. The relatively low activity of lipoprotein lipase in the heart and possibly in muscles of sand rats, the high enzymic activity in adipose tissue, and the lack of its reduction following fasting for 20 hours contribute toward channeling of lipoprotein triacylglycerols toward adipose tissue. Since in the sand rat adipose tissue free fatty acid synthesis is rather limited, the altered pattern of distribution and regulation of lipoprotein lipase may play an important role in the maintenance of the obesity syndrome under conditions of dietary affluence.

Metabolic response to starvation at late gestation in chronically ethanol-treated and pair-fed undernourished rats

To study the role of undernourishment in the negative effects of ethanol during pregnancy and to determine whether maternal ethanol intake modifies metabolic response to starvation at late gestation, female rats receiving ethanol in their drinking water before and during pregnancy (ethanol group) were compared with animals that received the same amount of solid diet as the ethanol group rats (pair-fed group) and with normal rats fed ad libitum (control group). All animals were killed on the 21st day of gestation, either in the fed state or after 24-hours fasting. The body weight of ethanol rats was lower than that of controls but higher than that of pair-fed rats. When compared with controls, ethanol and pair-fed rats had reduced fetal body weights, whereas fetal body length was reduced only in the former. In the fed state, blood glucose concentration was lower in the ethanol and pair-fed rats and fetuses than in controls. Twenty-four-hour starvation caused a reduction in this parameter only in control and ethanol mothers. In the fed state, maternal liver glycogen concentration was lower in ethanol and higher in pair-fed mothers than in controls. Blood β-hydroxybutyrate levels were higher in ethanol-treated mothers than in the others, and 24-hour starvation increased this parameter in ethanol and control rats to a greater extent than in the pair-fed ones. Liver triacylglyceride concentration was higher in ethanol-treated mothers than in the other two groups, and starvation caused this concentration to increase in ethanol and control groups but not in the pair-fed group. Maternal liver lipoprotein lipase activity did not differ among the groups when fed, but increased significantly with starvation in controls and ethanol-treated rats. Individual values of lipoprotein lipase activity in all the starved groups correlated with liver triacylglyceride concentrations. Results indicate that maternal undernourishment in ethanol-treated rats contributes to the negative effects of ethanol on fetal development in addition to certain other changes, such as the increase in maternal redox state and in circulating and liver triglycerides, directly related to ethanol oxidation. The intense maternal hypoglycemia observed in rats from the ethanol group could impair glucose availability to the fetus, and this situation would worsen with starvation. The higher hepatic glycogen levels in pair-fed mothers and their fetuses in the fed state as compared with the ethanol group, in spite of their similar hypoglycemia, seems to indicate a different metabolic adaptation in the two groups. A relationship is proposed in the starved condition between maternal liver lipoprotein lipase activity and changes in liver triacylglyceride and circulating ketone bodies in the three groups studied. The findings seem to indicate that, in spite of the metabolic disturbances produced by ethanol intake in the mother, the response to starvation in ethanol rats was similar to the one observed in controls, and different from the one in the pair-fed animals.

High liver lipoprotein lipase activity in hyperlipemic developing rats from undernourished pregnant mothers.

To study the potential relationship between circulating triacylglycerol (TAG) levels and lipoprotein lipase (LPL) activity in the newborn rat liver, pups from undernourished or normal control mothers were nursed by normal dams, and studied at 0, 1, 15 or 30 days of age. Plasma TAG levels and liver TAG concentration increased more in pups from undernourished mothers than they did in controls. At birth, liver LPL activity was similarly high in both groups but, whereas in controls it decreased progressively after birth, in pups from undernourished mothers it remained stable until 15 days of age. Results suggest that the hypertriglyceridemia present in pups from undernourished mothers may be responsible for the sustained high LPL activity in their liver which may enhance the hepatic uptake of circulating TAG.

Synthesis of lipoprotein lipase in the liver of newborn rats and localization of the enzyme by immunofluorescence.

In newborn rats, lipoprotein lipase (LPL) activity was higher in the liver than in several other tissues, such as heart, diaphragm or lungs, and accounted for about 3% of total LPL activity in the body. There was no significant correlation between LPL activity in liver and in plasma. Thus transport of the enzyme from extrahepatic tissues was probably not the major source of LPL in liver. To study LPL biosynthesis directly, newborn rats were injected intraperitoneally with [35S]methionine, and LPL was isolated by immunoprecipitation and separation by SDS/polyacrylamide-gel electrophoresis. Radioactivity in LPL increased with a similar time course in all tissues studied, including the liver. Substantial synthesis of LPL was also demonstrated in isolated perfused livers from newborn rats, whereas synthesis was low in livers from adult rats. There was strong LPL immunofluorescence in livers from newborn rats, mainly within sinusoids and along the walls of larger vessels. This labelling disappeared after perfusion with heparin, which indicates that much of the enzyme is in contact with blood and can take part in lipoprotein metabolism.

Effect of combined lipase deficiency ( cld/cld) on hepatic and lipoprotein lipase activities in liver and plasma of newborn mice

Combined lipase deficiency ( cld/cld) is a recessive mutation in mice which results in massive hyperlipemia and death within 3 days after birth. We studied the effect of this deficiency on lipolytic activities in liver and in pre- and postheparin plasma of mice less than 2 days old. Anti-hepatic lipase serum inhibited more than 85% of the lipolytic activity in liver and plasma of normal newborn mice when assayed in high-salt medium, validating the use of this medium for measuring hepatic lipase activity in mice. Anti-lipoprotein lipase serum, in contrast, inhibited only two-thirds of the lipolytic activity in liver and plasma when assayed in serum low-salt medium, and anti-hepatic lipase serum inhibited the rest. This indicates that assay with serum low-salt medium alone is not specific for lipoprotein lipase activity in mice. Therefore, immunoinhibition was used, as needed, for measuring lipoprotein lipase activity. The livers of unaffected newborn mice contained high levels of both hepatic and lipoprotein lipase activities, 228 and 187 mU/g, respectively. The plasma of unaffected mice contained a high level of hepatic lipase activity, 244 mU/ml, but practically no lipoprotein lipase activity. Heparin injected intraperitoneally increased plasma lipoprotein lipase activity to 152 mU/ml, but had no effect on plasma hepatic lipase activity, in unaffected mice. Hepatic lipase activity was virtually absent from both liver and plasma of cld/cld mice. Lipoprotein lipase activity was present in the liver at a surprisingly high level, 40% of that in normals, but was barely detectable in plasma. Heparin injection increased plasma lipoprotein lipase activity in cld/cld mice, but the increment was less than 10% of that in unaffected mice. Heparin had no significant effect on plasma hepatic lipase activity in defective mice. These findings confirm preliminary observations that hepatic lipase activity in liver and plasma and lipoprotein lipase activity in plasma are markedly reduced in combined lipase deficiency. The unexpected high level of lipoprotein lipase activity in liver of cld/cld mice suggests that regulation of lipoprotein lipase activity in liver of neonatal mice is different from that in other tissues.