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Biomedical subjects

G Ferland

Publications and source records attributed to G Ferland.

9 recordsLinked to original sources

Effect of dietary restriction on lysosomal bodies and total protein synthesis in hepatocytes of aging rats.

The accumulation of lysosomal bodies has long been considered to be an important correlate of aging. However it is not well established whether these age related changes interfere with cellular function. In this study, an evaluation of lysosomes by ultrastructural analysis was performed in livers of 4-6 and 20-24-month-old Sprague-Dawley female rats, fed ad libitum (A) or a restricted diet (R). An attempt was made to relate this parameter to hepatic protein synthesis, a liver function known to decrease with age and increase with dietary restriction. Aging was accompanied in both A and R animals with higher number and size of secondary lysosomes (lipofuscin) and by a decrease in total protein synthesis in hepatocytes. When compared to age matched ad libitum fed animals, livers of food restricted rats contained higher number of secondary lysosomes, yet exhibited higher protein synthetic capacity. Thus in hepatocytes, lipofuscin accumulation does not seem to interfere with cellular function.

Aging

Effect of dietary restriction on hepatic vitamin A content in aging rats.

The size and number of fat-storing cells (FSC), considered to be the main liver storage site of vitamin A, as well as hepatic vitamin A content, were studied in aging female Sprague-Dawley rats subjected soon after weaning to dietary restriction (R), that is, 60% of food consumed by their ad libitum-fed controls (A). In A or R rats, the FSC index (number of cells per 1000 hepatocytes) and volume density (% of hepatic volume) were increased significantly at 24-27 months compared with the younger age groups. The lipocyte index and volume density were also found to be significantly higher, after the first year, in R rats when compared to corresponding age-matched A controls. An increase in total vitamin A content was also noted with age in both groups. R rats exhibited higher retinol, retinyl ester, and total retinoid content than their corresponding controls, but the differences were statistically significant only at 12-14 and 24-27 months. These results indicate that, during aging, dietary restriction markedly increases vitamin A content in liver tissue, a change that may be relevant to the beneficial effect of this dietary manipulation on liver function.

Aging

Development of a diet low in vitamin K-1 (phylloquinone).

As part of a metabolic study aimed at inducing a subclinical vitamin K deficiency in healthy adults, we designed a diet containing less than 10 micrograms/day of vitamin K-1 (phylloquinone). Two-day menus were constructed from a vitamin K-1 food database developed in our laboratory. This diet offers palatability and provides nutrient adequacy; that is, it meets the Recommended Dietary Allowances for protein and all other vitamins and minerals. An interesting feature of the diet is that the vitamin K-1 level can be kept very low while still fulfilling a large range of energy needs (1,800 to 3,400 kcal/day). The diet proved useful in altering apparent nutritional status for vitamin K-1; after ingestion of the diet for 6 days, plasma concentrations of vitamin K-1 decreased by 80% and fell below the established normal range. Given the well documented drug-nutrient interaction between vitamin K and warfarin--a vitamin K antagonist routinely used in the management of thromboembolic diseases--the dietary information presented in this report may provide useful information for patients undergoing warfarin therapy.

Adult

Objective verification of dietary intake by measurement of urine osmolality.

A new method for assessing the accuracy of dietary nutrient intakes in metabolic studies is described. The theoretical basis of the method is the comparison of measurements of the urine osmole excretion rate (OER, the product of urine osmolality and urine weight) with values for OER predicted from dietary nitrogen, sodium, and potassium. The method was tested in 34 healthy male and female volunteers aged 18-78 y who made complete 24-h urine collections and consumed a diet over 6 d in metabolic-balance studies involving either overfeeding, weight maintenance, or weight loss. The coefficients of variation for equations relating measured OER to dietary nitrogen, sodium, and potassium intakes ranged from 14.1% for 1-d measurements to 6.94% for 6-d means. These results indicate that it should be possible to use measurements of the urine OER to identify dietary noncompliance in metabolic studies.

Adolescent

Characterization of liver lysosomal enzyme activity in hepatocytes, Kupffer and endothelial cells during aging: effect of dietary restriction.

The specific activity of 4 lysosomal enzymes was studied in homogenate, hepatocytes, Kupffer and endothelial cells isolated from the livers of female Sprague-Dawley rats aged 3.5, 12 and 24 months. Cells were obtained by enzymatic digestion and centrifugal elutriation. Cell viability was not affected by age or diet. In hepatocytes, the activities of all enzymes (acid phosphatase, beta-galactosidase, arylsulfatase B and cathepsin D) increased with age in rats fed ad libitum (A) but were not altered significantly by dietary restriction. The activities of all enzymes except acid phosphatase were systematically higher at 3.5 months of age in Kupffer and endothelial cells than in hepatocytes. Acid phosphatase, arylsulfatase B and cathepsin D activities increased with age in both Kupffer and endothelial cells. Beta galactosidase was decreased significantly with age in Kupffer cells but was elevated in endothelial cells. Rats exposed to dietary restriction (R) showed higher activities of beta-galactosidase, arylsulfatase B and cathepsin D when compared to corresponding A animals with the exception of the younger age group. No clear cut pattern was observed in acid phosphatase activity. Thus, the activities of liver lysosomal enzymes increase with age but the pattern of change differs with respect to enzyme and cell populations. The heightened enzyme activity in Kupffer and endothelial cells from R rats may reflect a more efficient phagocytic capacity in these animals.

Aging

Effect of aging and dietary restriction on bile acid metabolism in rats.

The aim of the present study was to determine whether increased output of phospholipid in bile during aging may be due to alteration of bile acid composition and stimulated hydrophobic bile acid formation. In female Sprague-Dawley rats we examined the influence of aging and life long dietary restriction (60% of the ad libitum intake) on bile flow, total bile acid secretion, bile acid composition and conjugation pattern, as well as phospholipid output. Rats were cannulated at 3.5, 8-12 and 24-27 months of age and bile collected for analysis. With age, there was a significant reduction in bile flow and total bile acid secretion, however, phospholipid output increased. Restriction of dietary intake exerted a beneficial effect on the age-related decline in bile formation. Studies of bile composition indicated that 12 alpha-hydroxylated bile acids (cholic acid and deoxycholic acid) secretion decreased in aged rats compared to 3.5-month-old rats. This was associated with a corresponding increase in secretion of chenodeoxycholic acid and hyodeoxycholic-ursodeoxycholic acid. However, the magnitude of the change in secretion of these bile acids could not account for the increased output of phospholipid in bile.

Aging

Dietary restriction influence bile formation in aging rats.

Food restriction is one of the most effective interventions which increases the survival of rodents and influences a variety of physiologic and pathologic processes. Thus, we examined whether life-long caloric restriction would influence bile formation, one of the important hepatic functions. Female Sprague Dawley rats were subjected soon after weaning to a restricted diet (60% of the diet consumed by the rats fed ad libitum) and bile formation determined at 3.5, 12 and 24 months of age. Rats had their bile ducts cannulated under nembutal anesthesia and bile collected at 10 min. intervals. Bile flow rate decreased 35% between 3.5 and 24 months of age. This decrease was associated with a reduction of the bile acid dependent fraction of bile flow (BADF) up to 12 months of age, thereafter the bile acid independent fraction (BAIF) also decreased. Phospholipid and cholesterol secretion rates increased with age, but did not correlate with bile acid secretion. In rats fed the restricted diet, bile flow was about 20% higher at 3-5 months of age when compared with the ad libitum fed group. This bile flow rate remained constant until 24 months of age. The increased bile flow was attributed to higher BADF and BAIF. The phospholipid and cholesterol secretion followed that of bile acids. It thus appears that dietary restriction exerts a beneficial effect on the age related decline in bile formation.

Aging