Diminished Weight Gain Research Articles

Subchronic neurotoxicity in rats of the structural fumigant, sulfuryl fluoride

Inhalation exposure of male and female Fischer 344 rats to sulfuryl fluoride [Vikane ® (Dow Chemical Company) gas fumigant] at 300 ppm for 6 hr/day, 5 days week, for 13 weeks caused diminished weight gain, dental fluorosis, a slight decrease in grooming, decreased flicker fusion threshold, slowing of flash, auditory and somatosensory evoked potentials, mild nasal and pulmonary inflammation, mild kidney effects, and mild vacuolation in the brain. Auditory brainstem responses (ABRs) and brain histology were evaluated two months postexposure in 2 male and 2 female rats. Both the ABRs and brain histology were within normal limits at this time, indicating that these treatment effects were, to at least a great extent, reversible. Exposure to 100 ppm resulted in dental fluorosis and very minor slowing of some evoked responses; all other measures, including brain histology, were normal. No treatment effects were noted at 30 ppm.

Portal vein blood insulin and glucagon are increased in experimental hyperthyroidism.

Decreased glucose tolerance in hyperthyroidism has been long recognized; however, the mechanism(s) responsible for altered carbohydrate metabolism have not been elucidated. Studies of insulin secretion in hyperthyroidism have been reported by several investigators; however, the results are not conclusive since hormone secretion has been reported as increased, normal, or decreased. Few investigations of glucagon secretion in hyperthyroidism have been described; thus, the role of the alpha cell hormone in the glucose intolerance associated with thyrotoxicosis has not been established. To clarify these matters, experimental hyperthyroidism was induced in male rats by injecting T4 ip for 9 days. On the 10th day, blood was collected from the portal vein for measurement of insulin and glucagon. Animals injected with T4 (500 microgram/kg . day) became clearly thyrotoxic as evidenced by elevated plasma T4 and T3 and diminished weight gain. Rats receiving 750 micrograms T4/kg demonstrated marked enhancement of pancreatic insulin and glucagon release as evidence by elevated portal vein hormone values. Plasma insulin and glucagon in T4-treated rats were substantially elevated regardless of whether the animals were fed or were fasted for 20 h before blood samples were obtained. Insulin and glucagon in vena cava blood were far lower than in the portal vein in both control and hyperthyroid rats, and there was no significant difference between the two groups. We believe that portal vein hormone concentrations more accurately reflect insulin and glucagon secretion than do peripheral blood levels because the hormones and partially degraded in the liver. It is postulated that elevated T4 stimulates the alpha cell to release excess amounts of glucagon, which enhances hepatic glucose output. The possible increase in hepatic glucose output plus insulin resistance, which is characteristic of hyperthyroidism, may account for a secondary rise in insulin release.

Altered fatty acid desaturation and microsomal fatty acid composition in the streptozotocin diabetic rat

AbstractStreptozotocin diabetes in the rat diminishes the synthesis of both monounsaturated and polyunsaturated fatty acids. Rat liver microsomal fatty acid composition and fatty acid desaturation were studied in the streptozotocin diabetic rat. The major alterations in fatty acid composition found in the diabetic rat were decreased proportions of palmitoleic, oleic and arachidonic acids and an increased proportion of linoleic and docosahexaeneoic acids. These findings, other than the increased docosahexaeneoic acid, probably result from the diminished liver microscomal δ9 and δ6 desaturase activities found in these animals. These changes are not due to the diminished weight gain of the diabetic animals since restricting food intake of control animals to achieve a similar weight gain failed to reproduce either the changes in fatty acid composition or the decrease in fatty acid desaturation. The increased food intake of the diabetic animal may contribute to the altered proportions of linleic and arachidonic acids since limiting food intake in diabetic animals to that of normal controls diminished the magnitude of these changes. Insulin therapy for 2 days not only reverses and overcorrects the diminished desaturase activities, but likewise reverses and overcorrects the altered fatty acid composition, with the exception of the diminished arachidonic aicd levels which are further decreased following insulin therapy. These findings strongly suggest that most of the changes in fatty acid composition in the diabetic rat are indeed caused by the diminished fatty acid desaturase activities.

Effects of Medium- and Long-Chain Triglyceride Diets in the Genetically Obese Zucker Rat

To test whether the property of medium-chain fatty acids (which have 6-12 carbon atoms) being incorporated only in small amounts into the various tissues of a living organism could be exploited to treat obesity, genetically obese Zucker rats and their lean littermates were fed a diet containing 20% medium-chain triacylglycerols (MCT) or long-chain triacylglycerols (LCT) for 10 weeks. MCT, as compared with LCT, had the following effects: 1) MCT did not diminish weight gain in either the nonobese or the obese rats; 2) they increased ketogenesis more in the former than in the latter; 3) they increased the concentration of triacylglycerols in the liver of the obese rats but not of the lean ones; 4) they decreased the concentration of cholesterol in the liver of the lean but not of the obese rats, and 5) they did not particularly affect the concentration of proteins, glucose and insulin in the blood. We therefore conclude that the influence of the genotype is much more important in the establishment of the biochemical characteristics of rats than is the nature of the fatty acids ingested. Replacing LCT in the diet with MCT did not correct any of the major metabolic disorders in obese rats and therefore cannot unaided constitute a solution to the problem of genetic obesity.

Respiratory toxicity of enzyme detergent dust

Cynomolgus monkeys exposed 6 hr daily, 5 days/week for 6 months to atmospheres containing synthetic detergent dust at 1, 10, or 100 mg/m 3 together with enzyme dust at 0.001, 0.01, 0.1, or 1 mg/m 3, or to the detergent dust alone at 100 mg/m 3, or to the enzyme dust alone at 1 mg/m 3. The enzyme was a mixture of two enzymes manufactured for use in commercial detergents: Novo Alcalase and Milezyme 8X. The mass median (aerodynamic equivalent) diameter of the dust particles was ⋍3 μm. No evident adverse effects were produced by any of the mixtures of 1 mg/m 3 detergent dust with as much as 0.1 mg/m 3 enzyme dust. The detergent dust alone at 100 mg/m 3 produced gross signs of respiratory distress, pulmonary histopathological effects, and pulmonary function impairment. This impairment, measured by the nitrogen washout method, was indicative of constricted small airways. Exposure to 10 or 100 mg/m 3 detergent dust together with 0.01 or 1 mg/m 3 enzyme dust produced the same effects along with diminished weight gain or weight losses. The 100 mg/m 3 level of detergent dust, alone and with enzyme, caused some mortality. At least one animal in each group exposed to enzyme dust had precipitating antibodies to the enzyme. Evidence of respiratory toxicity diminished greatly in animals that were held for 4 to 6 weeks after their last exposure to the dust, but single 6-hr reexposures of some of these animals reinstated many of their overt symptoms. The dust exposures had no apparent effects on total respiratory system flow resistance, diffusion capacity, hematology, clinical chemistry, urinalysis, intradermal or skin-prick challenge test results, or chest radiographs.

Effect on rat blood and aorta lipids of three edible oils (arachid, sunflower and primor) with low saturated fatty acid content.

Arachid, sunflower and primor oils, which are all poor in saturated fatty acids and differ, in particular, in their oleic, linoleic and linolenic acid content, were fed to rats throughout one short and one long experiment. In the short experiment (1 month), they were given a hyperlipidic diet (35% of total food weight) and in the long experiment (1 year) a normolipidic diet (6% of total food weight). The chief results observed were as follows. Diminished weight gain of rats ingesting sunflower oil in the long experiment when compared with the other two groups. Absence of significant differences in cholesterolemia, triglyceridemia and phospholipidemia, depending on the type of oil ingested. A significant rise in glycemia for rats absorbing sunflower oil in the short experiment, thus confirming our previous observations. A significant rise in blood urea in rats ingesting primor oil in the short experiment. A significant rise in proteinemia in rats absorbing primor oil in both experiments. Very similar fatty acid composition for serum triglycerides and free fatty acids, with a high linoleic acid content in animals absorbing sunflower oil (this only applied to the short experiment with a hyperlipidic diet). Identical fatty acid composition of serum phospholipids, which were also rich in stearic acid and to a lesser extent in arachidonic acid (this applied to all diets and experiments). Identical fatty acid composition of serum cholesterol esters, also rich in arachidonic acid, for all diets and experiments. Very similar fatty acid composition for aorta triglycerides and free fatty acids which, like the corresponding serum fractions, also had a high linoleic acid content in the sunflower oil group, in the short experiment (animals on a hyperlipidic diet). Identical fatty acid composition of aorta phospholipids whatever the diet or type of experiment. This composition is very similar that of serum phospholipids (i.e. particularly rich in stearic acid and fairly rich in arachidonic acid). A fatty acid composition for aorta cholesterol esters completely different from that of serum cholesterol esters, the first being rich in palmitoleate and laurate; the nature of this difference depends on the oil ingested, since palmitoleate was chiefly found in rats absorbing primor oil, and laurate in animals on the sunflower oil diet.

Studies on carbohydrate digestibility and weight gain response in rats fed dietary sucrose, glucose or fructose.

A study was made of carbohydrate digestibility and weight gain response in rats fed sucrose, glucose or fructose at varying levels in the diet. In a long-term experiment with older rats, sucrose-fed animals attained a greater mature weight than glucose and fructose-fed animals. In a digestibility study of shorter duration, animals fed sucrose and glucose diets had similar weight gains whereas fructose-fed animals showed a diminished weight gain response at higher levels of fructose in the diet. The digestible energy of glucose was observed to be significantly lower than that for either sucrose or fructose. Whereas the lower digestible energy of glucose may account for the lower weight gain on high glucose diets, a similar explanation is not valid for the response to fructose feeding. It would appear that an effect other than lowered feed intake or decreased digestibility is the cause of the lower weight gains observed on high fructose diets.