Increased plasma homocysteine concentration in rats from a low casein diet

Rats were fed on a 10% casein (10C) diet, 30% casein (30C) diet, 10C+0.5% methionine diet, or 30C+0.5% methionine diet for 14 d to investigate the relationship between the dietary protein level and plasma homocysteine concentration. The plasma homocysteine concentration was significantly higher in the rats fed on the 10C diet than in the rats fed on the 30C diet, and this phenomenon persisted even under the condition of methionine supplementation. The activity of hepatic cystathionine beta-synthase (CBS) was significantly lower in the rats fed on the 10% casein diets than in the rats fed on the 30% casein diets, irrespective of methionine supplementation. This is the first demonstration of a low-protein diet increasing the plasma homocysteine concentration in experimental animals. It is suggested that the decreased CBS activity might be associated, at least in part, with the hyperhomocysteinemia caused by the low-casein diet.     

Reset of the osmotic threshold for vasopressin in rats fed a low NaCl, K-free diet.

Activation of the renin-angiotensin system induced by feeding a low NaCl, K-free (LS) diet is associated with polydipsia and a chronic reduction in effective plasma osmolality (efPosm). We have recently shown that converting enzyme inhibition with enalapril (EP) abolishes polydipsia. The present study was designed to test the hypothesis that the osmotic threshold for vasopressin is reset in rats fed the LS diet and to examine the effect of EP on ambient and osmotically stimulated plasma vasopressin levels (PAVP). Animals were fed the LS diet or a control salt diet and treated with vehicle or the lowest dose of EP sufficient to prevent polydipsia (7.5 mg.kg-1.day-1) in rats fed the LS diet. PAVP and efPosm were measured under ambient conditions and after osmotic loading. Urine osmolality (Uosm) was measured under ambient conditions and after water loading. The chronic reduction in efPosm in LS rats was associated with the excretion of a Uosm 1-2 times greater than the corresponding Posm, PAVP similar to controls (LS, 2.27 +/- 1.08 vs. control, 1.19 +/- 0.22 pg/mL) and the ability to excrete a water load. Following osmotic loading, efPosm and PAVP increased significantly and similarly in both LS and control rats. EP administration had no effect on water intake, ambient efPosm and PAVP, and the AVP response to osmotic loading in rats fed the control diet. EP prevented polydipsia in LS rats, however it had no significant effect on ambient or osmotically stimulated PAVP or efPosm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pancreatic hydrolases in cold-induced hyperphagia of rats fed a low or high-fat diet

Rats fed either a low (2p. 100) or high (40 p. 100)-fat diet were exposed to 22 or 5 degrees C. The resulting hyperphagia adequately compensated energy losses as judged from body weight. The cold-induced hyperphagia was accompanied by a non-parallel increase in pancreatic hydrolases. Amylase and lipase were not increased above the adaptive levels they had respectively reached in the heat with a high-starch or high-lipid diet. Chymotrypsinogen, on the contrary, responded to increased intake of both diets. It also responded to the higher protein concentration in the high-fat diet caused by isocaloric replacement of starch by fat. Colipase varied independently of lipase and was increased additively by fat and protein intakes. Consequently, although limiting for lipase in the warm, colipase rose to a 1:1 ratio in the cold. Increased intake had a consistent pleiotropic effect evidenced by an increase of amylase with the high-fat diet and of lipase with the low-fat diet. The net effect was a significant increase in the lipid-digesting potential of the organism of lipid-fed animals upon exposure to cold, while the starch-digesting potential remained unaffected in starch-fed animals.     

Methionine and serine synergistically suppress hyperhomocysteinemia induced by choline deficiency, but not by guanidinoacetic acid, in rats fed a low casein diet

The effects of dietary supplementation with 0.5% methionine, 2.5% serine, or both on hyperhomocysteinemia induced by deprivation of dietary choline or by dietary addition of 0.5% guanidinoacetic acid (GAA) were investigated in rats fed a 10% casein diet. Hyperhomocysteinemia induced by choline deprivation was not suppressed by methionine alone and was only partially suppressed by serine alone, whereas it was completely suppressed by a combination of methionine and serine, suggesting a synergistic effect of methionine and serine. Fatty liver was also completely prevented by the combination of methionine and serine. Compared with methionine alone, the combination of methionine and serine decreased hepatic S-adenosylhomocysteine and homocysteine concentrations and increased hepatic betaine and serine concentrations and betaine-homocysteine S-methyltransferase activity. GAA-induced hyperhomocysteinemia was partially suppressed by methionine alone, but no interacting effect of methionine and serine was detected. In contrast, GAA-induced fatty liver was completely prevented by the combination of methionine and serine. These results indicate that a combination of methionine and serine is effective in suppressing both hyperhomocysteinemia and fatty liver induced by choline deprivation, and that methionine alone is effective in suppressing GAA-induced hyperhomocysteinemia partially.     

Morphometric analysis of skeletal response to vitamin D in uremic rats fed a low calcium diet.

The response of tibial metaphyses to pharmacologic levels of vitamin D in uremic rats fed a low calcium diet was evaluated morphometrically. Uremic (5/6 nephrectomized) rats given vitamin D had increased percent metaphyseal hard tissue, trabecular surface perimeter and percent trabecular osteoid surface and reduced numbers of osteoblasts and osteoclasts per millimeter of trabecular perimeter compared to either uremic rats given placebo or sham-operated rats given vitamin D. It was concluded that the resistance of metaphyseal trabeculae in uremic rats to vitamin D was due in part to the increase in osteoid-covered surfaces which inhibited osteoclasis and subsequent remodeling. The pathogenesis of worsening osteomalacia as a consequence of vitamin D administration to uremic rats on a low calcium diet remains unclear.     

Neuronal-glial interactions in rats fed a ketogenic diet

Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative metabolism of glucose as well as the increased astrocytic metabolism, may reflect adaptation of the brain to ketone bodies as major source of fuel.     

Nitrogen balance discrepancy in Wistar rats fed a cafeteria diet.

The nitrogen balance of Wistar rats aged 30-45 and 45-60 days fed either control or cafeteria diet has been determined by measuring the intake fecal and urinary excretion and nitrogen deposition in the body. The efficiency of extraction of dietary nitrogen was higher for cafeteria diet-fed rats, which showed a lower nitrogen excretion and higher body nitrogen accretion than controls. The accurate measurement of nitrogen intake, excretion and deposition showed a consistent proportion of nitrogen unaccounted for (10-26% of net intake) in the studied fractions, which proportion was higher in the youngest cafeteria diet-fed rats.     

Hepatic fatty acid-supported respiration in rats fed an energy-dense diet

The energy balance and hepatic fatty acid-supported respiration were studied in rats fed a control or an energy-dense diet. In addition, state 3 and 4 respiratory rates as well as ketone body production with palmitoylcarnitine as substrate were determined in isolated mitochondria. Metabolizable energy intake and energy expenditure increased in rats fed an energy-dense diet, but the gain in body weight and lipid content remained unchanged. No variation occurred in the mitochondrial palmitoylcarnitine utilization rate and ketone body production, but a significant increase in the mitochondrial content of ketone bodies and the serum levels was found in rats fed an energy-dense diet. Furthermore, we have shown a significant increase in fatty acid-stimulated respiration in hepatocytes from rats fed an energy-dense diet. The enhanced hepatic fatty acid utilization as an energy substrate found in rats fed an energy-dense diet may contribute to reduce the availability of lipids for storage, thus counteracting the development of obesity.     

Absorption of oligo-L-[35S]methionine after feeding of a low casein or a low soybean protein isolate diet in rats.

We studied the absorptive properties of oligo-L-methionine (OM), which is an enzymatically synthesized and slowly digestible peptide. Previously, we demonstrated that when OM was added to a low casein diet, the improvement of the body weight gain was higher than when OM was added to a low soybean protein isolate (SPI) diet and we suggested that the difference in the supplementary effect of OM depends on its absorptive rate. In the present study, the OM absorption estimated by the portovenous difference in radioactivity derived from 35S-labeled OM was higher in the casein diet than in the SPI diet in early stages of feeding after fasting. Absorbed OM was quantified by subtracting the radioactivity of [35S]OM remaining in the whole gut from the ingested [35S]OM, 90 and 180 min after feeding casein and SPI diets containing 3% [35S]OM. We also estimated the absorptive efficiencies by subtracting the amount of radioactivity remaining in the intestines from the amount of [35S]OM emptied from the stomach as percentages of the emptied OM. Both the amount of absorbed OM and absorptive efficiencies of OM were higher in the casein group than in the SPI group, and the higher absorptive efficiency in the casein group indicates a higher digestibility for OM when rats are fed a 3% OM diet after fasting. The digestibility of [35S]OM measured by fecal excretion of radioactivity of OM during normal feedings for diets containing 0.3% [35S] OM for 7 days was about 80% in the casein group and 60% in the SPI group. We conclude that the different supplementary effects of OM in the low casein and SPI diets depend on the difference in OM digestibility. The difference in the digestibility of OM may partly depend on the faster absorption rate of OM in the early stages of feeding.     

Copper metabolism in analbuminaemic rats fed a high-copper diet

Copper metabolism in male Nagase analbuminaemic (NA) rats was compared with that in male Sprague Dawley (SD) rats fed purified diets containing either 5 or 100 mg Cu/kg diet. Dietary copper loading increased hepatic and kidney copper concentrations in both strains to the same extent, but baseline values were higher in the NA rats. There was no strain difference in true and apparent copper absorption nor in faecal endogenous and urinary copper excretion. NA rats had higher levels of radioactivity in kidneys at 2 hr after intraperitoneal administration of ⁶⁴Cu. As based on the distribution of added ⁶⁴Cu, about 70% of plasma copper appeared to be in the non-protein compartment in the NA rats, whereas in SD rats, it was only about 1%. It is concluded that the NA rats are able to maintain a relatively normal metabolism of copper, even after dietary copper challenge. In the NA rats, zinc concentrations in kidneys, liver and urinary zinc excretion were elevated when compared with SD rats. The high-copper diet did not affect tissue zinc concentrations and apparent zinc absorption in both strains of rats.     

Burn-induced oxidative stress is altered by a low zinc status: kinetic study in burned rats fed a low zinc diet

As an initial subdeficient status of zinc, considered as an essential antioxidant trace element, is frequent in burned patients, we aim to assess the effects of low zinc dietary intakes on burn-induced oxidative stress, in an animal model. After 8 weeks of conditioning diets containing 80 ppm (control group) or 10 ppm of zinc (depleted group), Wistar rats were 20% TBSA burned and sampled 1-10 days after injury. Kinetic evolutions of zinc status, plasma oxidative stress parameters, and antioxidant enzymes were also studied in blood and organs. The zinc-depleted diet induced, before injury, a significant decrease in zinc bone level and the increase of oxidative stress markers without stimulation of antioxidant enzyme activity. After burn, more markedly in zinc depleted animals than in controls, zinc levels decreased in plasma and bone, while increasing in liver. The decrease of thiol groups and GSH/GSSG ratio and the depression of GPx activity in liver are also moderately emphasized. Nevertheless, depleted zinc status could not be considered as determining for oxidative damages after burn injury. Further investigations must also be done to enlighten the mechanism of beneficial effects of zinc supplementation reported in burned patients.