Replacement of long-chain triglyceride with medium-chain triglyceride/long-chain triglyceride lipid emulsion in patients receiving long-term parenteral nutrition: effects on essential fatty acid status and plasma vitamin K1 levels

BACKGROUND: In long-term parenteral nutrition (LTPN) patients, the use of a 50:50 mixture of medium- and long-chain triglyceride emulsion (MCT/LCT) has been suggested to prevent or correct fatty liver infiltration. However, the use of MCT/LCT lipid emulsion results in a 50% reduction of essential fatty acids and vitamin K1 supply and could induce essential fatty acid and vitamin K1 deficiencies. This study evaluated the effect of a long-term infusion of MCT/LCT lipid emulsion on plasma fatty acid (FA) and vitamin K1 levels on LTPN patients. METHODS: In a prospective nonrandomized crossover study, we measured plasma phospholipid FA composition by gas chromatography and vitamin K1 levels by high-performance liquid chromatography in 11 LTPN patients before and after a 4-month replacement of the usual 20% LCT lipid emulsion (20% Lipoven; Fresenius-Kabi France, Sèvres, France) by a 20% MCT/LCT lipid emulsion (Medialipide B; Braun Medical, Boulogne, France). RESULTS: Patient received LTPN for 46 +/- 40 months; IV lipid emulsion was 827 +/- 336 mL/week. MCT/LCT lipid substitution did not change most of the essential plasma fatty acid concentrations and did not induce essential fatty acid deficiency. With both lipid emulsions, the triene/tetraene (20:3n-9/20:4n-6) ratio remained within the normal ranges. However, with MCT/LCT lipid emulsion, 22:4n-6 (LCT: 0.50 +/- 0.12; MCT/LCT: 0.63 +/- 0.11%) and 22:5n-6 (LCT: 0.32 +/- 0.11; MCT/LCT: 0.48 +/- 0.15%) increased significantly (p = .022 and 0.011, respectively). Plasma vitamin K1 levels decreased drastically with MCT/LCT lipid emulsion. CONCLUSIONS: An amount of 2.85 +/- 1.55 g x kg(-1) week(-1) of MCT/LCT lipid emulsion neither induced essential fatty acid deficiency nor improved the fatty acid disturbances usually observed in LTPN patients but did induce a drop in plasma vitamin K1 levels.     

L-carnitine improves glucose disposal in type 2 diabetic patients

OBJECTIVE: Aim of the present study is to evaluate the effects of L-carnitine on insulin-mediated glucose uptake and oxidation in type II diabetic patients and compare the results with those in healthy controls. DESIGN: Fifteen type II diabetic patients and 20 healthy volunteers underwent a short-term (2 hours) euglycemic hyperinsulinemic clamp with simultaneous constant infusion of L-carnitine (0.28 micromole/kg bw/minute) or saline solution. Respiratory gas exchange was measured by an open-circuit ventilated hood system. Plasma glucose, insulin, non-esterified fatty acids (NEFA) and lactate levels were analyzed. Nitrogen urinary excretion was calculated to evaluate protein oxidation. RESULTS: Whole body glucose uptake was significantly (p<0.001) higher with L-carnitine than with saline solution in the two groups investigated (48.66+/-4.73 without carnitine and 52.75+/-5.19 micromoles/kg(ffm)/minute with carnitine in healthy controls, and 35.90+/-5.00 vs. 38.90+/-5.16 micromoles/kg(ffm)/minute in diabetic patients). Glucose oxidation significantly increased only in the diabetic group (17.61+/-3.33 vs. 16.45+/-2.95 micromoles/kg(ffm)/minute, p<0.001). On the contrary, glucose storage increased in both groups (controls: 26.36+/-3.25 vs. 22.79+/-3.46 micromoles/kg(ffm)/minute, p<0.001; diabetics: 21.28+/-3.18 vs. 19.66+/-3.04 micromoles/kg(ffm)/minute, p<0.001). In type II diabetic patients, plasma lactate significantly decreased during L-carnitine infusion compared to saline, going from the basal period to the end-clamp period (0.028+/-0.0191 without carnitine and 0.0759+/-0.0329 with carnitine, p<0.0003). CONCLUSIONS: L-carnitine constant infusion improves insulin sensitivity in insulin resistant diabetic patients; a significant effect on whole body insulin-mediated glucose uptake is also observed in normal subjects. In diabetics, glucose, taken up by the tissues, appears to be promptly utilized as fuel since glucose oxidation is increased during L-carnitine administration. The significantly reduced plasma levels of lactate suggest that this effect might be exerted through the activation of pyruvate dehydrogenase, whose activity is depressed in the insulin resistant status.     

Diversity of insulin resistance in monkeys with normal glucose tolerance

Insulin resistance has been proposed as a critical factor in the development of Type II diabetes, hypertension, dyslipidemia, and coronary artery disease. However, even in normal healthy individuals, a wide range of in vivo insulin action has been found. In the present study we sought to examine this heterogeneity in insulin action in both normal and spontaneously obese nonhuman primates. Maximal insulin responsiveness as measured by a hyperinsulinemic euglycemic clamp, fasting plasma glucose, and insulin levels, beta-cell insulin response to glucose, glucose tolerance, and adiposity were measured in 22 male rhesus monkeys. Results showed that lean animals (body fat < or = 22%) had higher insulin-stimulated glucose uptake (M rate: 14.42+/-1.8 mg/kg FFM/min) compared to obese (8.08+/-0.8). The obese monkeys, with 23-49% body fat, had a wide range of M values (5.32-14.29 mg/kg FFM/min) which showed no relationship to degree of adiposity. In all monkeys, M values had a strong inverse correlation with fasting plasma insulin levels (r=-0.76; p<0.001), but not with fasting glucose or glucose disappearance rate. We conclude that neither degree of obesity above a critical threshold nor range of glucose tolerance is related to insulin resistance; however, in individuals with normal glucose tolerance an early reliable indicator of defective insulin action appears to be fasting insulin concentration. Longitudinal determination of basal insulin levels obtained under standardized conditions so as to minimize extraneous variability is likely to strengthen the ability to predict insulin resistance and possible later development of overt Type II diabetes.     

Total nutritional manipulation in humans: report of a cancer patient

We report here on a patient requiring home total parenteral nutrition (TPN) for a huge intra-abdominal desmoid associated with chronic small bowel pseudo-obstruction who was kept on a special lipid-based calorie regimen for 5 months. The rationale was to attempt to feed the host with a minimal stimulation of tumour growth by using lipid as caloric substrate instead of glucose which is utilized by the tumour. Gluconeogenesis was tentatively inhibited at the level of phosphoenolpyruvate-carboxy-kinase through the oral intake of hydrazine sulphate. The regimen consisted of 28 non-protein lipid Kcal/kg/day plus 1.5 g amino acid per kg/day. Only a small amount of glucose (approx. 40 g/day) was allowed. Tolerance to the regimen was good and body weight maintained. Liver enzymes remained within the normal range and liver sonography was normal throughout the 5 months' therapy and there were no episodes of symptomatic hypoglycaemia. The tumour volume did not substantially change.     

Whole-body and adipose tissue glucose metabolism in response to short-term fasting in lean and obese women

BACKGROUND: Alterations in glucose metabolism during early fasting may be an important trigger of the hormonal and metabolic responses to fasting. OBJECTIVE: The purpose of this study was to determine whether glucose metabolism in response to brief starvation differs in lean and abdominally obese women. DESIGN: We evaluated whole-body glucose metabolism by use of stable-isotope tracer methods and glucose uptake in subcutaneous abdominal adipose tissue by use of arteriovenous balance in 7 lean [58 +/- 2 kg; body mass index (BMI; in kg/m(2)): 21 +/- 5] and 6 abdominally obese (96 +/- 2 kg; BMI: 36 +/- 1) women after 14 and 22 h of fasting. RESULTS: Between 14 and 22 h of fasting, whole-body glucose production and disposal declined in both groups (P < 0.05), but the reduction was 50% greater in lean than in obese women (P < 0.05). The decline in glucose uptake at 22 h of fasting was also lower in obese (0.11 +/- 0.04 micromol*100 g(-1) x min(-1)) than in lean (0.26 +/- 0.03 micromol x 100 g(-1) x min(-1)) women (P < 0.05). Decreases in plasma insulin and leptin concentrations between 14 and 22 h of fasting were also lower in obese than in lean women (insulin: 20 +/- 3% and 32 +/- 5%; leptin: 18 +/- 3% and 37 +/- 6%; both P < 0.05). CONCLUSIONS: The normal decline in glucose production and uptake that occurs during early fasting is blunted in women with abdominal obesity. These alterations in glucose metabolism are associated with a blunted decline in circulating concentrations of both insulin and leptin, which may explain some of the differences in the metabolic response to fasting observed between lean and abdominally obese persons.     

Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients

In vitro and in vivo animal studies have reported strong insulin-like or insulin-potentiating effects after cinnamon administration. Recently, a human intervention study showed that cinnamon supplementation (1 g/d) strongly reduced fasting blood glucose concentration (30%) and improved the blood lipid profile in patients with type 2 diabetes. The objective of this study was to investigate the effects of cinnamon supplementation on insulin sensitivity and/or glucose tolerance and blood lipid profile in patients with type 2 diabetes. Therefore, a total of 25 postmenopausal patients with type 2 diabetes (aged 62.9 +/- 1.5 y, BMI 30.4 +/- 0.9 kg/m2) participated in a 6-wk intervention during which they were supplemented with either cinnamon (Cinnamomum cassia, 1.5 g/d) or a placebo. Before and after 2 and 6 wk of supplementation, arterialized blood samples were obtained and oral glucose tolerance tests were performed. Blood lipid profiles and multiple indices of whole-body insulin sensitivity were determined. There were no time x treatment interactions for whole-body insulin sensitivity or oral glucose tolerance. The blood lipid profile of fasting subjects did not change after cinnamon supplementation. We conclude that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes. More research on the proposed health benefits of cinnamon supplementation is warranted before health claims should be made.     

Prevention of total parenteral nutrition-induced cholestasis by low non-protein energy supply: an animal experiment and clinical study

30 cecum-ligated rats were divided into 3 groups: group OS fed with stock diet; group HTPN (high-energy total parenteral nutrition) infused with 260 kcal/kg/d of non-protein energy (NPE), which was isoenergetic to the first group; and group LTPN (low-energy total parenteral nutrition) infused with 160 kcal/kg/d. All rats received approximately 1.4 g/kg/d of nitrogen. Positive nitrogen balances were obtained in all 3 groups, although the values were lower in group LTPN. Serum albumin remained normal. Total bilirubin, lipoprotein-X, alkaline phosphatase (AKP), gamma-glutamyl trans-peptidase (gamma-GT) and glutamic-pyruvic transminase (GPT) were significantly lower in group LTPN than in group HTPN. Histological examination with both light and electron microscopy revealed more severe bile stasis in the canaliculi in group HTPN than in group LTPN. In a separate clinical study, lasting more than 4 weeks, two groups of surgical patients received isonitrogenous TPN regimes containing different amounts of energy (40 kcal/kg/d and 30 kcal/kg/d, respectively). 40% of the NPE was infused as fat. The patients were matched for age, clinical condition and nutritional support technique. There were no differences between the groups in nitrogen balance or serum albumin. However serum AKP and gamma-GT increased in the HTPN group after 2 weeks of nutritional support, whilst in the LTPN group the increase did not occur until the fourth week. Our results suggest that TPN-induced cholestasis can be prevented or delayed by reducing the intake of NPE.     

Beneficial metabolic effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in healthy obese women

BACKGROUND: Although a regular meal pattern is recommended for obese people, its effects on energy metabolism have not been examined. OBJECTIVE: We investigated whether a regular meal frequency affects energy intake (EI), energy expenditure, or circulating insulin, glucose, and lipid concentrations in healthy obese women. DESIGN: Ten women [x +/- SD body mass index (in kg/m(2)): 37.1 +/- 4.8] participated in a randomized crossover trial. In phase 1 (14 d), the subjects consumed their normal diet on 6 occasions/d (regular meal pattern) or followed a variable meal frequency (3-9 meals/d, irregular meal pattern). In phase 2 (14 d), the subjects followed the alternative pattern. At the start and end of each phase, a test meal was fed, and blood glucose, lipid, and insulin concentrations were determined before and for 3 h after (glucose and insulin only) the test meal. Subjects recorded their food intake on 3 d during each phase. The thermogenic response to the test meal was ascertained by indirect calorimetry. RESULTS: Regular eating was associated with lower EI (P < 0.01), greater postprandial thermogenesis (P < 0.01), and lower fasting total (4.16 compared with 4.30 mmol/L; P < 0.01) and LDL (2.46 compared with 2.60 mmol/L; P < 0.02) cholesterol. Fasting glucose and insulin values were not affected by meal pattern, but peak insulin concentrations and area under the curve of insulin responses to the test meal were lower after the regular than after the irregular meal pattern (P < 0.01 and 0.02, respectively). CONCLUSION: Regular eating has beneficial effects on fasting lipid and postprandial insulin profiles and thermogenesis.     

Effects of a Rubus coreanus Miquel supplement on plasma antioxidant capacity in healthy Korean men

Korean raspberry, Rubus coreanus Miquel (RCM), contains high concentrations of phenolic compounds, which prevent oxidative stress. To determine the effect of RCM on antioxidant capacity in humans, we assessed in vivo lipid oxidation and antioxidant enzyme activities from plasma in 15 healthy men. The subjects ingested 30 g of freeze-dried RCM daily for 4 weeks. Blood was taken at baseline and at the end of the study to determine blood lipid profiles, fasting plasma glucose, liver function, lipid peroxidation, and antioxidant enzyme activities. RCM supplementation had no effect on blood lipid or fasting plasma glucose concentrations but decreased alkaline phosphatase activity. RCM supplementation increased glutathione peroxidase activities (P < 0.05) but had no effect on lipid peroxidation. These results suggest that short-term RCM supplementation may offer health benefits by enhancing antioxidant capacity in a healthy population.     

Endotoxin-mediated hepatic lipid accumulation during parenteral nutrition in rats

OBJECTIVE: To assess the effect of endotoxemia on hepatic lipid content during parenteral nutrition (PN) in rats. METHODS: Twenty male Sprague-Dawley rats (185-230 gm) were randomized to receive PN (n=9) or PN plus a continuous infusion of E. coli 026:B6 lipopolysaccharide (LPS; n= 11). All animals received isocaloric (170 kcal/kg/day), isonitrogenous (1.1 g N/kg/day), glucose-based PN for the next 78 hours. After 30 hours of adaptation to TPN, the animals were randomized to receive PN or PN plus LPS at 6 mg/kg/day for the remaining 48 hours of study. The animals were euthanized and the livers were harvested. RESULTS: Liver weight increased significantly (by 60%) from 7.5+/-0.6 g to 12.1+/-2.4 g (p < or = 0.01) in the animals who received PN versus LPS, respectively. The proportion of liver water remained the same for PN and LPS groups (72.9+/-3.2% versus 72.3+/-3.8%, respectively, p = N.S.). However, liver fat increased disproportionately (by about 130%) from 0.20+/-0.05 g to 0.46+/-0.20 g (p < or = 0.01) total fat weight or from 9.6+/-1.8% to 13.6+/-4.1% (p < or = 0.02) lipid content (g/g) of the dry liver weight for the PN and LPS groups, respectively. CONCLUSION: Endotoxin, when given concomitantly with parenteral nutrition, increases hepatic lipid accumulation and thus augments the development of parenteral nutrition-associated fatty liver in rats.     

Metabolic responses to lipid infusions in patients with liver cirrhosis

Energy expenditure, whole body substrate oxidation rates and arterial substrate concentrations were measured in 14 patients with liver cirrhosis and 13 control subjects before and during sequential infusions of a long chain (LCT) or a medium chain triglyceride emulsion (MCT) without and with concomitant insulin plus glucose infusions. Resting energy expenditure, basal substrate oxidation rates and the arterial concentrations of glucose, lactate, triglycerides and ketones were normal, whereas plasma free fatty acids and glycerol were both increased in patients with liver cirrhosis. The arterial plasma triglyceride and free fatty acid concentrations as well as whole body lipid oxidation rate rose in response to LCT in both groups and the maximum lipid oxidation rate was 1.1 or 1.3 mg/kg fat free mass x min in controls and in cirrhotics, respectively (n.s.). Concomitantly, glucose oxidation rate fell to 65% of basal values in controls (p < 0.01), but remained nearly unchanged in the cirrhotic group (89% of the basal value; n.s.). The increase in plasma ketones was reduced to 67% of control values in liver cirrhosis (p < 0.01). Only a slight effect on energy expenditure was observed in both groups. When compared to controls, liver cirrhosis impaired insulin-induced increases in glucose disposal (-30%, p < 0.01) and in non oxidative glucose metabolism (-93%, p < 0.01). Concomitantly, normal increases in energy expenditure, glucose oxidation rate and the arterial plasma lactate concentrations and normal decreases in lipolysis, lipid oxidation and ketogenesis were observed in patients with liver cirrhosis. When lipids were given together with glucose, energy expenditure and lipid oxidation increased in controls, but glucose was the preferred fuel oxidised and lipid-induced thermogenesis was reduced in the cirrhotic group. Using a 50% MCT-emulsion, plasma free fatty acid concentrations further increased, but energy expenditure and lipid oxidation remained unchanged in both groups and further increases in plasma ketones were only observed in controls. Infusing glycerol in a subgroup of patients showed no thermogenic effect and a reduced glycerol clearance in liver cirrhosis.     

Impaired glucose tolerance is not associated with lipid intolerance

Post-prandial (pp) hypertriglyceridaemia (HTG) has an important role in the development of atherosclerosis in Type 2 diabetes. Impaired glucose tolerance (IGT) is associated with an increased risk of atherosclerosis and increased level of fasting triglycerides (TG). The aim of this study was to analyse pp HTG and the composition of TG-rich lipoproteins in carefully selected subjects with IGT in comparison to controls with normal glucose tolerance (NGT). Fifteen men with IGT and 27 men with NGT, aged 44 to 70 yr, were examined. All study participants were non-smokers and had fasting TG <4.6 mmol/l. The subjects underwent an oral glucose tolerance test (75 g glucose) and a lipid-glucose tolerance test (LGTT; 92 g fat, 126 g carbohydrate), that allowed the assessment of lipid and glucose tolerance in one test. HbA1C, plasma glucose and lipids were measured by routine methods. Lipoprotein subfraction analysis of VLDL (VLDL1: Sf60-400 and VLDL2: Sf20-60) was conducted in a fasting state, as well as 4 hr after the LGTT using a density gradient ultracentrifugation with a subsequent compositional analysis. No significant difference was found either for fasting or pp TG, or for area under curve (AUC) -TG (12.21 +/- 4.27 mmol/l x 6 hr vs 13.95 +/- 6.74 mmol/l x 6 hr; p>0.05) between the IGT and NGT. A highly significant correlation was found between the fasting TG and the AUC-TG (r=0.925; p<0.01). To avoid bias by differences in fasting plasma TG known to affect lipid tolerance we investigated 11 matched pairs for fasting TG. Also, the matched-pairs evaluation pp TG course did not differ significantly from the IGT and NGT. No significant difference for fasting or pp levels of VLDL1 and VLDL2, or for the TG content of chylomicron, VLDL1 and VLDL2 and for the percentage of TG in VLDL1 and VLDL2 was found between the IGT and NGT group. In conclusion, IGT subjects with a similar level of fasting TG do not exhibit lipid intolerance. Our data suggest that glucose intolerance should precede lipid intolerance.     

Ameliorating effects of water-soluble polysaccharides from woody ear (Auricularia auricula-judae Quel.) in genetically diabetic KK-Ay mice

We investigated the ameliorating effects of the three groups of water-soluble polysaccharides, a mixture of crude polysaccharides (FA), acidic polysaccharide fractions (FA-A), and neutral polysaccharide fractions (FA-N), obtained from the hot water extracts of the fruit bodies of Auricularia auricula-judae Quel. In genetically diabetic KK-Ay mice from 6 to 11 weeks of age. Male mice were divided into five dietary groups: 1) control group, given a basal diet; 2) FA group, given an FA diet (15 g FA/kg diet); 3) FA-A group, given an FA-A diet (8 g FA-A/kg diet); 4) low FA-N group, given a low FA-N diet (2 g FA-N/kg diet); and 5) high FA-N group, given a high FA-N diet (8 g FA-N/kg diet). Compared with the control diet, FA supplementation had significant effects in lowering fasting and nonfasting blood glucose, HbA1c, urinary glucose, food intake, and water intake. FA administration also improved glucose tolerance to intraperitoneal glucose loading, but it did not affect the nonfasting insulin level. FA-N supplementation had dose-dependent effects in lowering fasting and nonfasting food glucose, insulin, HbA1c, urinary glucose, food intake, and water intake. However, the glucose tolerance was not ameliorated by either the low or the high FA-N diet. FA-A administration showed no beneficial effects in KK-Ay mice.     

Antioxidant effect of zinc,selenium and their combination on the liver and kidney of alloxan-induced diabetes in rats

Zinc and selenium have been shown to singly act in normalising glycaemia and are also postulated to possess insulin-like functions. Supplementation with their combination in the diets of rats with alloxan-induced diabetes was investigated with the aim of investigating their effects on glucose homeostasis and their antioxidant properties on the liver and kidney of alloxan-induced diabetic rats. Thirty-five rats were randomly assigned to five groups and four groups were made diabetic by the administration of 150 mg/kg body weight of alloxan monohydrate, after which three diabetic groups were fed with diets supplemented with zinc, selenium and a combination of the two. Zinc, selenium and the combination significantly reduced blood glucose concentration, restored hepatic functions, increased the antioxidant status of the diabetic rats and reduced lipid peroxidation in both the hepatic and renal tissues. It was concluded that supplementation with zinc, selenium and the combination facilitated glucose uptake, prevented oxidative stress, reduced lipid peroxidation and preserved hepatic function in diabetes.     

Hepatic de novo lipogenesis after liver transplantation

BACKGROUND: The liver can synthesize fatty acids from carbohydrate (de novo lipogenesis [DNL]). We hypothesized that stimulation of this process may be involved in the development of obesity and dyslipidemia, 2 conditions frequently encountered after liver transplantation. METHODS: Hepatic fractional DNL and glucose metabolism were measured in 2 groups of 5 patients (age 36.8 +/- [SD] 14.9 years, BMI 26.3+/-5.3 kg/M2) 1 to 5 years after liver transplantation and 8 healthy subjects (age 28.1+/-5.3 years, BMI 27.2+/-4.5 kg/M2). Subjects were studied while receiving an isoenergetic nutrition (based on 1.1 x their basal energy expenditure) as hourly oral liquid formula during 10 hours. Their hepatic DNL was measured by infusing 1-13C acetate and measuring tracer incorporation in VLDL-palmitate. Their glucose metabolism was assessed by means of 6,6-2H2 glucose and indirect calorimetry. RESULTS: Two liver transplant recipients and 4 healthy subjects were obese, as defined by a BMI > 27 kg/M2. Fractional hepatic DNL was not different in the 2 groups of subjects: liver transplant recipients 3.1+/-1.7% vs 3.2+/-2.1% in healthy subjects. In both groups, DNL increased in proportion to BMI. When both groups were analyzed together, BMI was positively correlated with DNL (DNL = 0.28 x BMI - 4.28, r2 = .445, p < .05). Whole body glucose turnover was 15.0+/-4.4 micromol/kg per minute in liver transplant recipients and 15.8+/-4.1 micromol/kg per minute in healthy subjects (NS). Net carbohydrate oxidation tended to be lower in liver transplant recipients (8.1+/-2.6 micromol/kg per minute) than in healthy subjects (10.4+/-2.4 micromol/kg per minute; NS). Net nonoxidative glucose disposal (4.0+/-2.7 in liver transplant recipients vs 1.9+/-1.8 in healthy subjects, NS) and energy expenditure (0.065+/-0.01 vs 0.065+/-0.01 kJ/kg per minute) were similar in both groups. CONCLUSIONS: These results indicate that fractional hepatic DNL is not altered by liver transplantation during near continuous nutrition. The disposal of orally administered carbohydrate is also essentially unchanged. This strongly argues against a role of hepatic DNL in the pathogenesis of obesity and dyslipidemia after liver transplantation.     

Effect of adrenalectomy on liver lipid content of fasted rats.

The interrelationship between thyroid and adrenal hormones in the regulation of lipid accumulation of the liver during fasting was examined with the use of intact, sham operated and adrenalectomized (ADX) rats previously fed a high carbohydrate diet. Adrenalectomy depressed the lipid accumulation of the liver induced by fasting. This was restored by cortisone administration, but not by epinephrine injection. Lipid content of the liver during fasting tended to be decreased in rats made hyperthyroid by intraperitoneal injection of thyroxine compared to euthyroid-fasted rats. In rats made hypothyroid by oral administration of propylthiouracil, liver lipid content during fasting was significantly higher than that of euthyroid-fasted rats. These responses of liver lipid to thyroid activity were minimized in ADX rats. Cortisone tended to restore completely the liver response to thyroid activity. The maximal response of liver lipid to cortisone was obtained in hypothyroid-ADX rats. The injection of epinephrine alone did not cause any significant change in liver lipid content of ADX rats regardless of the thyroid status. These findings suggest that glucocorticoid must be present for thyroid function to exert its effect on the lipid accumulation of the liver induced by fasting.     

Hypocaloric lipid emulsions and amino acid metabolism in injured rats

The present study was designed to determine the degree and mechanism by which administration of medium-chain triglyceride emulsions spare body protein after injury. Forty male rats underwent venous catheterization and received nonsterile bilateral femur fractures. All rats received 2.5 g/day amino acids and either no additional calories (group I) or 20 kcal/day of either glucose (group II), a long-chain triglyceride emulsion (group III), a medium-chain triglyceride emulsion (group IV), or a structured lipid emulsion composed of 40% sunflower oil and 60% medium-chain triglycerides (group V). The diets were administered for 3 days, and rates of plasma leucine flux, oxidation, and incorporation into protein as well as tissue protein synthetic rates in liver and muscle were measured using the constant infusion of L-[1-14C]leucine. Results demonstrated that the administration of glucose or various lipid emulsions improved cumulative nitrogen balance significantly when compared to a diet containing amino acids alone. In addition, the administration of glucose or lipid emulsions significantly stimulated protein synthesis in liver and muscle. Moreover, a structured lipid emulsion of medium- and long-chain fatty acids produced significant increases in liver protein synthesis greater than that observed with either glucose or long-chain triglyceride emulsions. We conclude that added energy as fat or glucose reduces net protein catabolism and improves tissue protein synthesis in these injures rats and that lipid emulsions are as effective as dextrose. A structured triglyceride emulsion synthesized from medium- and long-chain fatty acids appears to better support hepatic protein synthesis.     

Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver.     

Evaluation of the nature of brain tumors using methods of nuclear medicine]

FDG-PET studies permit an assessment of the degree of brain tumour malignancy and detection of tumour recurrence. MIBI-SPECT also affords promising results in this respect. In this work, the diagnostic value of MIBI-SPECT was compared with that of FDG-PET for the determination of primary brain tumours malignancy and the detection of recurrent brain tumours. SPECT and PET examination were carried out within a week in 14 patients (12 males, 2 females, mean age: 40 years, range 16-61 years) with brain tumours. Seven patients had a primary tumour, and in a further 7 MRI or the clinical signs and symptoms let to a suspicion of tumour recurrence. All tumours were verified histologically to be gliomas of grades I-IV. The SPECT and PET images were analysed visually and semiquantitatively. In 3 of the investigated 7 primary glioma patients, there was a visibly enhanced MIBI-positive cases, only one had an increased FDG uptake. In 4 of the 7 tumour recurrence cases, either the MIBI or the FDG uptake was visibly increased. All of these were histologically high-grade gliomas. In the remaining low grade tumours (primary of recurrent), neither MIBI nor FDG revealed a pathologically increased uptake. The intensity of radiopharmaceutical uptake at the site of the tumours was visually and semiquantitatively higher for MIBI that for FDG. It is concluded that MIBI-SPECT is a valuable and simple tool for evaluation of the biological characteristics of brain tumours, showing increased uptake of MIBI according to the malignancy and tumour recurrence of brain tumours.     

The dose-dependent effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract, liver, and pancreas of the rat.

The effects of single oral administration of saline suspensions of chrysotile A to fasting male albino rats on DNA synthesis in the GI tract, pancreas, and liver were studied after a subsequent interval of 3 days. Incorporation of [³H]TdR was elevated in the whole stomach, duodenum, and jejunum following administration of chrysotile in the dose range of 5 to 100 mg/kg; incorporation in the liver was, however, reduced. There was no change in pancreatic and colonic [³H]TdR uptakes following administration of chrysotile. Preliminary data suggest that physicochemical alterations of chrysotile by gastric acid may influence its subsequent effects on DNA synthesis.