Hepatic Lipogenic Enzyme Activities Research Articles

Effect of dried Bacillus subtilis culture on growth, body composition and hepatic lipogenic enzyme activity in female broiler chicks.

To investigate the effect of dried Bacillus subtilis culture on growth, body composition and hepatic lipogenic enzyme activity, female broiler chicks were fed on either no additive (control) or dried B. subtilis-culture-supplemented commercial diets (215 g crude protein/kg, 12.85 MJ metabolizable energy/kg) at 10 or 20 g/kg diet for 28 d from 14 to 42 d of age. Body weight, and moisture, fat, protein and ash contents of the body were not influenced by the B. subtilis culture. Feed efficiency, N utilization, the ratio of abdominal fat or liver to body weight, acetyl-coenzyme A carboxylase (EC 6.4.1.2) activity, liver and serum cholesterol contents were significantly lower in treatment groups, while fatty acid synthetase activity and serum cholesterol concentration were not significantly different, compared with the control group. Liver triacylglycerol concentration was decreased in chicks given 20 g culture/kg diet, while serum and carcass triacylglycerol concentrations were significantly lower in treatment groups than in the control group. Serum phospholipid concentration was increased but carcass phospholipid concentration was decreased in chicks given 20 g B. subtilis/kg diet, while liver phospholipid concentration was not significantly influenced. The advantages of inclusion of B. subtilis to the broiler diet included improved feed efficiency, less abdominal fat, reduced triacylglycerol concentrations in the liver, serum and carcass and reduced cholesterol concentrations in the liver and carcass.

Polyunsaturated fatty acid regulation of lipogenic enzyme gene expression in liver of genetically obese rat.

The polyunsaturated fatty acid regulation of lipogenic enzyme gene expression in genetically obese rats (Wistar fatty, non-insulin-dependent diabetes mellitus) has been investigated. The hepatic mRNA concentrations and activities of lipogenic enzymes in the fatty and lean rat were greatly increased by feeding a hydrogenated fat diet to fasted rats, and also reached similar maximum levels with similar time courses. By feeding a corn oil diet, however, the increases were markedly reduced in the lean rats, but were not significantly reduced in the fatty rats. Consequently, when the animals were fed corn oil, the mRNA concentrations and activities in the fatty rats were higher than those in the lean. Thus, it appeared that the higher gene expression in the fatty rats can be ascribed to the defects of polyunsaturated fatty acid suppression. On the other hand, insulin binding to receptors in the liver was reduced by the corn oil diet in the lean rats but was not reduced in the fatty rats (although the insulin binding level was lower in the Wistar fatty rats than in the lean). Changes in the insulin receptor autophosphorylation and kinase activity toward exogenous substrate were similar to the insulin binding. It is suggested that the polyunsaturated fatty acids may not suppress insulin binding activity to receptors in the livers of the fatty rats, probably due to down regulation by hyperinsulinemia. The defects of polyunsaturated fatty acid suppression of lipogenic enzyme gene expression may be one of the factors of obesity.

Effects of vanadate administration on the high sucrose diet-induced aberrations in normal rats.

Effects of feeding sucrose rich diet supplemented with and without the insulinmimetic agent vanadate for a period of six weeks were studied in rats. Sucrose diet caused hypertriglyceridemia (140% increase), hyperinsulinemia (120% increase) and significant elevations in the levels of glucose (p < 0.001) and cholesterol (p < 0.05) in plasma as compared to control starch fed rats. Activities of hepatic lipogenic enzymes, ATP-citrate lyase, glucose 6-phosphate dehydrogenase and malic enzyme increased by 100-150% as a result of sucrose feeding. However, glycogen content and the activities of glycogen synthase and phosphorylase in liver remained unaltered in these animals. The plasma levels of triacylglycerols and insulin in the rats fed on vanadate supplemented sucrose diet were 65% and 85% less, respectively as compared to rats on sucrose diet without vanadate. The concentrations of glucose and cholesterol in plasma and the activities of lipogenic enzymes in liver did not show any elevation in sucrose fed rats when supplemented with vanadate. These data indicate that the sucrose diet-induced metabolic aberrations can be prevented by the insulin-mimetic agent, vanadate.

Effects of high sucrose diet on insulin-like effects of vanadate in diabetic rats.

The insulin-like effects of vanadate were compared in streptozotocin-induced diabetic rats fed on high starch control and high sucrose diets for a period of six weeks. Diabetic rats in both diet groups were characterized by hypoinsulinemia, hyperglycemia (6.8-7.0 fold increase) and significant decreases (p < 0.001) in the activities of glycogen synthase, phosphorylase and lipogenic enzymes, ATP-citrate lyase, glucose 6-phosphate dehydrogenase and malic enzyme in liver. There were no diet-dependent differences in these abnormalities. However, the insulin-mimetic agent vanadate was more effective in diabetic rats fed sucrose diet as compared to animals fed control starch diet. Vanadate administration resulted in 30% and 64% decreases in plasma glucose levels in diabetic rats fed control and sucrose diets, respectively. The activities of glycogen synthase (active) and phosphorylase (active and total) were restored significantly by vanadate in control (p < 0.05-0.01) and sucrose (p < 0.001) diets fed diabetic rats. This insulin-mimetic agent increased the activities of hepatic lipogenic enzymes in control diet fed rats to 38-47% of normal levels whereas in sucrose fed group it completely restored the activities. Sucrose diet caused a distinct effect on the plasma levels of triacylglycerol (4-fold increase) and apolipoprotein B (2.8-fold increase) in diabetic rats and vanadate supplementation decreased their levels by 65-75%. These data indicate that vanadate exerts insulin-like effects in diabetic rats more effectively in sucrose fed group than the animals fed control diet. In addition, vanadate also prevents sucrose-induced hypertriglyceridemia.

Changes in hepatic lipogenic enzyme activities in voles and mice treated with monosodium aspartate

Changes in activities of hepatic lipogenic enzymes, atp citrate lyase and acetyl-CoA carboxylase, were measured in voles and C57BL mice following neonatal administration of monosodium aspartate ( msa). Hepatic lipogenic enzyme activities in voles were considerably lower than those in mice; these low activities were considered to be one of the characteristics of voles as a herbivore. In the msa-treated voles and mice, the plasma insulin concentrations increased significantly. The msa-treated mice showed remarkable obesity and increased lipogenic enzyme activities. In the msa-treated voles, signs of obesity were not observed and hepatic atp citrate lyase activity increased significantly; acetyl-CoA carboxylase activity did not increase.

Mechanisms of triglyceride-lowering effect of an HMG-CoA reductase inhibitor in a hypertriglyceridemic animal model, the Zucker obese rat.

Inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase have been approved for treatment of hypercholesterolemia in humans. This class of therapeutic agents, in addition to lowering plasma cholesterol, reduces plasma triglyceride levels. We have investigated the mechanism of triglyceride-lowering effect of lovastatin in the hypertriglyceridemic state by using a rodent model of hypertriglyceridemia and obesity, the Zucker obese (fa/fa) rat. Lovastatin treatment (4 mg/kg), as compared to placebo, caused a 338% reduction in plasma triglyceride (146 +/- 5 vs. 494 +/- 76 mg/dl), a 58% decrease in total cholesterol (99 +/- 13 vs. 156 +/- 18 mg/dl), and a 67% reduction in high density lipoprotein (HDL)-cholesterol (69 +/- 8 vs. 115 +/- 15 mg/dl). The fall seen in plasma triglyceride was due to a decrease in hepatic secretion of very low density lipoproteins (VLDL), determined after blocking the clearance of triglyceride-rich lipoproteins with Triton WR-1339. Lovastatin treatment did not affect either the activities of hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, or malic enzyme, or the activities of the lipolytic enzymes of adipose tissue, lipoprotein lipase, or liver, hepatic triglyceride lipase. Supplementation of mevalonolactone in the diet partially reversed the changes in plasma triglyceride (265 +/- 37 vs. 146 +/- 5 mg/dl), but not in total or HDL-cholesterol. These data demonstrate that, in the hypertriglyceridemic Zucker rat model, HMG-CoA reductase inhibitors reduce the rate of secretion of VLDL and this effect can be partially reversed by administration of mevalonolactone.

Changes in hepatic metabolism through simulated weightlessness: decrease of glycogen and increase of lipids following prolonged immobilization in the rat.

The effect of simulated weightlessness on hepatic metabolisms of carbohydrates and lipids was investigated in rats that were chronically immobilized by means of a suspension harness. During the 10-day period of the suspension, the animals showed a substantial decrease in the hepatic glycogen content, whereas the content of hepatic total lipids was markedly elevated. Similar results were obtained when the "suspended" animals were provided with a regular amount of nutrients by a force-feeding procedure. In the suspended animals, hepatic parenchymal cells were filled with large fat droplets, and hepatic triglyceride contents were elevated. The prolonged immobilization led to a slight, but significant, increase in glucose-6-phosphatase activity in the liver, suggesting that an increased glycogen breakdown might have occurred in the suspended animals. However, it was unlikely that the increased amount of glucose produced by the glycogen breakdown was utilized as a substrate for the lipogenesis in the liver, because hepatic lipogenic enzyme activities were unaffected by the suspension. The results suggest that the hepatic lipids accumulate in animals exposed to a prolonged immobilization state, presumably due to a decreased lipolysis and/or a suppressed lipoprotein mobilization from the liver into the blood stream.

Insulin-like effect of vanadate on malic enzyme and glucose-6-phosphate dehydrogenase activities in streptozotocin-induced diabetic rat liver

The effect of oral administration of sodium orthovanadate on hepatic malic enzyme (EC 1.1.1.40) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) activities was investigated in nondiabetic and diabetic rats. Streptozotocin-induced diabetic rats were characterized by 4.7-fold increase in plasma glucose and 82% decrease in plasma insulin levels. The activities of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were also diminished ( P < 0.001). Vanadate treatment in diabetic rats led to a significant decrease ( P < 0.001) in plasma glucose levels and to the normalization of enzyme activities, but it did not alter plasma insulin levels. In nondiabetic rats vanadate decreased the plasma insulin level by 64% without altering the enzyme activities. Significant correlation was observed between plasma insulin and hepatic lipogenic enzyme activities in untreated and vanadate-treated rats. Vanadate administration caused a shift to left in this correlation suggesting improvement in insulin sensitivity.

Lipogenesis in vivo in prematurely weaned rats

Male, Sprague-Dawley rats were weaned on postnatal day 17 to a semi-purified diet in which fat supplied 10% of the energy. Compared with rats allowed to wean spontaneously to the same maternal diet, prematurely weaned rats showed elevations in hepatic glucose-6-phosphate dehydrogenase and malic enzyme activities by postnatal day 20; the activities of both enzymes peaked on postnatal day 25. Lipogenesis in vivo, estimated by using 3H 2O as a tracer, increased slowly in the liver and carcas of spontaneously weaned animals. In contrast, premature weaning led to increases in lipogenesis in both compartments. Hepatic lipogenesis in prematurely weaned rats, whether expressed in terms of radioactivity or as a fraction of total synthesis, peaked at the age of 20 days. The results suggested that the elevations of hepatic lipogenic enzyme activities which occur in prematurely weaned rats probably reflect increased demand for NADPH.

Comparative studies on lipogenic enzyme activities in brown adipose tissue and liver of the rat during starvation-refeeeding transition and cold exposure

1. 1. The effect of starvation-refeeding transition and cold exposure on the activity of lipogenic enzymes in brown adipose tissue (BAT) and liver from rats was compared. 2. 2. Starvation caused a decrease of lipogenic enzyme activities in BAT and liver. 3. 3. Refeeding of the animals with a high carbohydrate diet caused an increase of lipogenic enzymes in these tissues. 4. 4. Cold exposure (4°C for 30 days) led to the increase of BAT enzyme activities to the values observed in rats fed a high carbohydrate diet. 5. 5. Under the same conditions the activity of hepatic lipogenic enzymes also increased but never reached the values observed in the liver of rats fed with a high carbohydrate diet. 6. 6. Therefore BAT and liver lipogenic enzymes showed, in general, a similar pattern of variation under identical nutritional conditions, but substantial differences between these two organs occurred as far as the response to cold exposure was concerned. 7. 7. The experiments also revealed that in the control animals BAT displayed a higher lipogenic potential than the liver.

Effects of dietary sucrose on the activities of hepatic lipogenic enzymes in perinatally undernourished mature rats

Male, Sprague-Dawley rats were reared in litters of 9 or 18 pups. At the age of 60 days, they were challenged with a diet containing sucrose for 14 days. Rearing in large litters was associated with significant decreases in the activities of hepatic malic enzyme and glucose-6-phospahte dehydrogenase; ATP-citrate lyase activity showed a similar tendency to diminish. Dietary sucrose led to increased enzyme activities, but there was no evidence of interaction between litter size and dietary sucrose. This suggested that neonatal food restriction may not necessarily impair the ability of the animal to respond to certain dietary stimuli later in life.

Lipid lowering effect of omega-3 fatty acids in genetically obese zucker rats

Omega-3 fatty acids (n-3 FA) are known to reduce blood lipid levels. Recent data, however, suggested that n-3 FA supplementation may worsen glycemic control in diabetic humans. This study was designed to explore the effects of n-3 FA feeding on lipid metabolism and glycemic control in a strain of genetically obese, hyperlipidemic rats. Lean and obese Zucker rats were fed a semi-purified diet made with either n-3 FA or corn oil (n-6, 10% w/w for both diets). After 16 weeks feeding, lean and obese rats fed the n-3 FA diet showed a significant reduction in blood triglyceride (TG) levels. Obese rats had significantly elevated TG levels in comparison with lean rats. Lean n-3 FA fed rats had elevated lipoprotein lipase activity in adipose tissue while hepatic triglyceride lipase activity was lowered by n-3 FA feeding in both lean and obese rats. Hepatic lipogenic enzyme activities were suppressed by fish oil feeding. However, fish oil feeding significantly increased hepatic gluconeogenic enzyme activity in lean rats. Therefore, n-3 FA feeding may exert different effects on blood lipid and glucose levels in lean and obese subjects.

Effect of Fish Oil Diet on Activities of Lipogenic Enzymes and Glucose -6 -phosphatase in Rat Liver and Adipose

In order to evaluate the effect of fish oil on lipid hydrogenase(G6PDH), malic enzyme(ME), glucose-6-phosphatase(G6Pase) activities were measured in liver and adipose tissue of rats fed 13 days supplemented fish oil at the level of 10% (W/W). Two other groups of rats were fed 10% soybean oil or lard to compare with the effect of fish oil. In all groups, activities of hepatic G6PDH and ME were depressed from the beginning of feeding. This effect was greatest (50%) in fish oil group. Hepatic G6Pase was highest in rats fed lard. When the level of fish oil was reduced to half, as total fat content was maintained at the level of 10% by complementary lard, lipogenic enzyme depressing effect of fish oil was as significant as shown in 10% fish oil diet. Hepatic G6PDH was depressed significantly (14%) in rats fed fish oil as low as 2%. On the other hand, changes in adipose tissue G6PDH and ME activities were small. Adipose tissue G6PDH activity increased slightly in rats fed with increasing fish oil(above 0.5%). It is suggested that fish oil alter, more markedly than either soybean oil or lard, cellular lipid metabolism by reducing activities of hepatic lipogenic enzymes.

Hepatic Fatty Acid Synthesis and Triglyceride Secretion in Rats Fed Fructose- or Glucose-Based Diets Containing Corn Oil, Tallow or Marine Oil

The effects of three dietary fats, corn oil (CO), tallow (T) and marine oil (MO), on serum triglycerides, hepatic lipogenic enzyme activity and lipogenesis in vivo using 3H2O were measured in fed and fasted rats that had been consuming diets in which the carbohydrate was either glucose or fructose. Hepatic triglyceride secretion was also measured in fasted rats fed the same diets. In both the fed and fasted state, hepatic enzyme activity and lipogenesis in vivo were greater in fructose-fed rats than in glucose-fed rats and less in both CO- and MO-fed rats than in T-fed rats. In rats fed glucose, serum triglycerides were lower in fasted rats fed MO than in fasted rats fed CO. In rats fed glucose or fructose, hepatic triglyceride secretion was lower in rats fed MO than in those fed CO or T.

Effects of fat intake on body composition and hepatic lipogenic enzyme activities of hamsters shortly after exercise cessation

Effects of fat intake on body composition and lipogenic enzyme activities were examined in hamsters. Forty-two female hamsters were randomly divided into two groups of 21 each. One group had access to voluntary disc running; the other group was sedentary. All were fed a low-fat, high-carbohydrate diet. After 30 d, seven hamsters from each group were killed and all running activity was discontinued. Remaining hamsters were separately assigned to two groups of seven and fed either a low-fat or high-fat diet for 7 d and then killed. Voluntary running increased food intake and weight gain and reduced body fat (52%). Cessation of exercise greatly enhanced body fat gain. High-fat diet enhanced weight gain. Increased energy intake during postexercise period appeared to cause enhanced body fat gain. The high-fat diet suppressed lipogenic enzyme activities. Serum triglyceride, total cholesterol, and HDL cholesterol levels were not affected by exercise or cessation of exercise.

Developmental changes in hepatic fructose 2,6-bisphosphate content and phosphofructokinase-1 activity in the transition of chicks from embryonic to neonatal nutritional environment.

Within 2 days of hatching in chicks, there are parallel increases in hepatic fructose 2,6-bisphosphate content and phosphofructokinase-1 activity. The changes observed are a consequence of feeding on the carbohydrate-rich diet of neonatal life: lack of access to food after hatching prevents changes for either parameter. The results are discussed in relation to changes in the activities of hepatic lipogenic enzymes during the embryonic/neonatal transition of chicks and the role of insulin in co-ordination of developmental processes.

Modulation of the Exercise and Retirement Effects by Dietary Fat Intake in Hamsters

An experiment was conducted to determine the effects and interactions of exercise-retirement and dietary fat Intake on body composition and hepatic lipogenic enzyme activities in hamsters. Forty-eight adult female hamsters were randomly allotted to eight groups of six each for a 40-d experiment. Exercise was in the form of voluntary wheel-running. Four groups served as either exercise or sedentary controls and were fed either a low or a high fat diet for 40 d, in a factorial fashion. Another four groups had access to exercise for 32 d and were then retired for 8 d. Of these four groups, two were fed either the low or high fat diet for the entire 40-d period; the other two were changed to the other diet on d 32. Results showed that compared to sedentary hamsters, exercise hamsters had greater body weight gain but less body fat content and hepatic lipogenic enzyme activities. Under both sedentary and exercise conditions, high fat-fed hamsters had lower hepatic lipogenic enzyme activities and less body fat content than low fat-fed hamsters. Upon retirement, high fat feeding led to a faster increase in body fat especially in previously high fat-fed hamsters. Results of this study suggest that dietary fat intake can significantly modulate the exercise and retirement effects with respect to body weight gain and body fat content.

The effect of feeding maltulose and lactulose on hepatic lipogenic enzyme activities in the rat

The effect of feeding maltulose, lactulose, and sucrose (ketose disaccharides) and maltose and lactose (aldose disaccharides) on hepatic lipogenic enzyme activities in the rat was studied. Male Sprague-Dawley rats were starved for 2 days and refed for 2 days diets containing 45% total carbohydrate. Lactulose and lactose were fed at a level of 15% of the diet due to their poor digestibility. Activities of hepatic glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) were measured. Hepatic G6PD and ME activities in rats fed maltulose were similar to rats fed maltose. Hepatic ME activity was lower in rats fed maltulose than sucrose. Rats fed lactulose had lower G6PD and ME activities than rats fed lactose. The atudy suggests that in the rat lactulose is less utilizable than lactose, and that maltulose is less lipogenic than sucrose.

Changes in the activities of hepatic lipogenic-related enzymes and in the concentrations of various plasma and liver lipid fractions in hens before and after the onset of laying.

The changes in the concentrations of various plasma and liver lipid fractions, plasma E2 and corticosterone, and hepatic lipogenic related enzyme (LRE) activities, were determined. The relationships between the concentrations of these plasma hormones and hepatic lipoge-nesis around the onset of egg production were elucidated.E2 concentration rose gradually as the hens advanced in age, reaching a peak at the age of 150 days which was the period immediately before the onset of egg laying. Triglyceride, NEFA, total cholesterol and phospholipid levels in the plasma remained relatively constant between 90 and 140 days of age. These rose rapidly as the birds neared the age of 150 days, and reached their peaks immediately before the onset of laying. These values decre-ased, and then remained stable, upon the onset of egg production; nevertheless, even at their reduced levels, they were still comparatively higher than these obtained during the 90-140 days of pre-ovulation period.Hepatic triglyceride content rose gradually and simulataneously with the aging of the hens and reached a peak immediately before the onset of laying. It decreased when the egg laying set in, but remained at a relatively higher level thereafter.The activities of hepatic LREs increased gradually as the hens advanced in age. Fatty acid synthetase reached a peak at 130 days of age and citrate cleavage enzyme and NADP-malate dehydro-genase, 140 days of age.Statistically significant positive correlations were observed between plasma E2 concentra-tion and the grouped parameters of abdominal fat weight (P<0.01), hepatic triglyceride content (P<0.01), concentrations of various plasma lipid fractions (P<0.01), and activities of fatty acid synthetase (P<0.05), NADP-malate dehydrogenase (P<0.05) and citrate cle-avage enzyme (P<0.05) in the liver of hens.

Effect of dietary medium chain triglyceride on lipogenic enzyme activity in rat liver.

This study was conducted to confirm that medium chain triglyceride (MCT) feeding itself would increase hepatic lipogenic enzyme activity without causing a lack of essential fatty acids (EFA) in the liver. Male weaning rats were fed for 11 weeks on diets containing 2% corn oil and 13% various fats: MCT, corn oil, tripalmitin or beef tallow, respectively. MCT feeding was clearly shown to increase the activities of fatty acid synthetase (FAS) and malic enzyme (ME) in the liver. Rats weighing 170 g were pair-fed for 7 days on diets containing 15% MCT, 13% MCT + 2% corn oil, 15% corn oil, and 2% corn oil and no fat (control groups), respectively, under a fixed level of carbohydrate (sucrose). The addition of 2% corn oil to MCT (13%) did not depress these enzyme activities, even though supplementing the fat-free diet with 2% corn oil resulted in a significant decline in the activities. When the rats received various amounts of MCT, the extent to which the degree of FAS and ME activities increased by MCT feeding depended on the amount of MCT in the dietary fat mixture with corn oil. Supplement of over 5% corn oil to MCT diets did not inhibit them sufficiently. In the liver lipids of animals fed MCT, there were no appearances of 20:3 omega 9 (5,8,11-eicosatrienoic acid), but the levels of mono-unsaturated fatty acids were increased by MCT feeding. The results suggest that MCT ingestion itself enhances lipogenic enzyme activity via some metabolic charge.