Biochemical and ultra-structural reactions to parenteral nutrition with two different fat emulsions in rats.

OBJECTIVE: To compare the effects on fat metabolism and Kupffer cell morphology by total parenteral nutrition (TPN) with two different fat emulsions. DESIGN: Thirty-two male Sprague-Dawley rats, divided into three groups, were investigated. Rats fed orally were used as a reference group, and a group of rats receiving TPN with fat emulsions containing pure long-chain triglycerides (LCT) was compared to a group of rats receiving fat emulsions containing both long-chain triglycerides and medium-chain triglycerides (MCT/LCT). The TPN regimens were equicaloric and administered continuously via a jugular catheter for 10 days. INTERVENTIONS: After suffocation, blood of the rats was collected for the determination of serum lipids. Epididymal fat and heart were collected for the analysis of lipoprotein lipase (LPL) activities, and liver specimens were saved for analyses of hepatic triglyceride concentration, as well as activities of hepatic lipase (HL) and lysosomal enzymes. Light and electron microscopy were used for examination of the Kupffer cell reaction. RESULTS: Directly after termination of parenteral feeding, the levels of serum triglycerides and high density lipoprotein (HDL) triglycerides were higher in the MCT/LCT group than in the LCT group, while no differences concerning cholesterol and phospholipid concentrations were found. No significant difference in liver steatosis was found between the two TPN groups. Comparison of the TPN groups showed that the MCT/ LCT group had significantly decreased LPL activity in adipose tissue, while the LCT group had significantly increased LPL activity in the heart. The activity of HL was low in both groups, but significantly lower in the LCT group. Lipid accumulation and an increased number of lysosomes were found in all Kupffer cell when TPN with LCTemulsions was used. Moreover, TPN induced a pronounced increase in various liver lysosomal enzyme activities, but there was no notable difference between LCT and MCT/LCT effects. CONCLUSIONS: Compared to treatment with pure LCTemulsions, treatment with MCT/LCT emulsions evoked weaker biochemical reactions in terms of lower activity of lipoprotein lipase in fat and heart together with higher serum and HDL triglyceride levels. Morphological signs of increased Kupffer cell activity such as the appearance of multiple lysosomes and fat vacuoles in the cytoplasm followed treatment with pure LCT emulsions. However, both TPN groups showed a marked increase in activities of liver lysosomal enzymes.

The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients.

Pyridoxine and folic acid supplementation in dialysis patients is a matter of debate. This study was performed to estimate the effects of pharmacologic doses of these vitamins on serum lipid and plasma homocysteine concentrations, which are known to be high in dialysis patients. Both hemodialysis and continuous ambulatory peritoneal dialysis patients were included in the study. Pyridoxine supplementation had a mild but significant cholesterol-lowering effect (7%). Folic acid supplementation significantly lowered plasma homocysteine concentrations by a mean of 30%. There was a strong, inverse correlation between blood folate and plasma homocysteine concentrations. These results indicate that daily supplementation with pyridoxine 300 mg and folic acid 5 mg has a beneficial effect on the cardiovascular risk profile in dialysis patients.

Pyridoxine reduces cholesterol and low-density lipoprotein and increases antithrombin III activity in 80-year-old men with low plasma pyridoxal 5-phosphate.

We have previously observed that pyridoxine treatment reduced plasma total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations and increased antithrombin III (AT III) activity in atherosclerotic patients with subnormal plasma pyridoxal 5-phosphate (PLP) levels. In order to confirm these results, we selected 17 males with low plasma PLP levels from a group of 122 80-year-old males in whom PLP has been determined. After supplementation with 120 mg of pyridoxine per day for 8 weeks their mean plasma TC and LDL cholesterol concentrations were decreased by 10% (p less than 0.01) and 17% (p less than 0.001), respectively. There was no effect on high-density lipoprotein cholesterol and triglycerides but plasma AT III activity was increased by 6% (p less than 0.05). The mechanism by which pyridoxine acts is unclear but it is hypothesized that pyridoxine-derived PLP may enhance the catabolism of LDL and the activity of AT III by inhibiting their glycosylation.

Plasma lipoproteins, liver function and glucose metabolism in haemodialysis patients: lack of effect of L-carnitine supplementation.

The effects of L-carnitine administration (2 g i.v. three times weekly for 6 weeks) were studied in a double blind trial comprising 2 X 14 patients on regular haemodialysis treatment. The initial plasma carnitine concentrations were normal in the male, but slightly lowered in the female participants and rose more than ten-fold in the patients receiving active treatment. The majority (15/28) of patients had moderate hypertriglyceridaemia, whereas plasma HDL cholesterol levels were normal. Activities of hepatic and lipoprotein lipase were decreased and fat tolerance impaired. The S-triiodothyronine and/or thyroxine levels were subnormal in 11 patients. Four patients had fasting hyperinsulinemia, and 6 demonstrated abnormal B-glucose patterns after a peroral glucose load. The galactose elimination rate demonstrated moderately impaired hepatocyte function in four patients. No effects of carnitine treatment on any of the variables could be detected.

Microcalorimetric studies on the total metabolic activity of fat cells.

We have applied microcalorimetry to the study of total cellular metabolic activity by direct registration of heat production from small samples of isolated fat cells. The cellular heat production is rapidly influenced by addition of hormones and substrates in vitro; e.g. glucose and insulin increases heat production two- to three-fold. The perirenal fat had the highest heat production. Fat cell thermogenesis decreases with age (and increasing mean fat cell size) of the rat. Obese patients had low heat production measured in gluteal adipocytes; the cellular thermogenesis increased, but did not fully normalize, on weight reduction. In combination with measurements of substrate and metabolite concentrations, microcalorimetry allows a detailed quantitative assessment of energy metabolism in the cell, which makes it a powerful tool for the study of adipose tissue metabolism under physiological and pathophysiological conditions.

The effect of D,L-carnitine supplementation on muscle metabolism, neuropathy, cardiac and hepatic function in hemodialysis patients. A pilot study.

Three patients on regular hemodialysis treatment were perorally supplemented with D.L-carnitine, 900 mg/d, during four weeks. Before treatment, muscle carnitine concentrations were low and the patients showed signs of hypometabolism in skeletal muscle, cardiomyopathy, impaired hepatic function and a moderate hyperlipoproteinemia. After treatment, the skeletal muscle metabolism normalized. The results further indicate improvement of the cardiac and hepatic function and of the neuropathy on the sensory side. No improvement was found, however, in plasma lipoprotein pattern or in variables reflecting plasma lipid transport (lipoprotein lipase activity and intravenous fat tolerance).

Wheat bran increases high-density-lipoprotein cholesterol in the rat.

1. Five groups of male Sprague Dawley rats were given for 6 months a diet with high protein and fat contents but a very low dietary fibre content (group B), and this diet mixed with (g/kg) 50 low-methoxyl pectin (group L), 50 high-methoxyl pectin (group H), 50 guar gum (group G) and 200 wheat bran (group WB, corresponding to 100 wheat fibre) respectively. 2. The weight increment was significantly lower in group G than in the other groups. Assuming no energy value of the dietary fibre, the weight increment (/kJ) was the same in groups B, L and H, lower in group G and higher in group WB, indicating that a proportion of the bran fibre might in fact be available as a source of energy. 3. Wheat bran increased total plasma cholesterol and high-density-lipoprotein cholesterol after 6, 12 and 26 weeks. Group G had significantly lowered plasma cholesterol after 12 weeks. Pectin on the other hand did not significantly influence total or HDL-cholesterol levels. It is therefore possible that the plasma cholesterol lowering effect of pectin previously demonstrated in the rat is dependent on the presence of significant amounts of dietary cholesterol as our diets did not contain added cholesterol. Plasma triglycerides decreased with age but were similar in all groups.