Injection Of Gold Thioglucose Research Articles

Rate of Incorporation of Dietary Fat in Gold Thioglucose Obesity in Mice

Gold Thioglucose injections in mice are followed by a rapid accumulation of fat in the carcasses. The incorporation of an oral dose of [3H] glyceroyl tripalmitate in body fat stores showed after GTG-treatment a transient but significant increase and a return to normal values within 6 weeks. The rate of incorporation of dietary fat into the body was estimated from these values as well as from food intake and fat content of the diet (2.5 per cent). The resulting curve showed great similarity with the first differential of the curve of total body fat accumulated during that period. The rate of incorporation of dietary fat into body stores is apparently modified in GTG obesity in mice.

The identification of gold in the brain of the mouse following gold-thioglucose administration

The early lesion and resulting glial scar induced in the brains of mice by injections of gold-thioglucose have been studied at the light- and electron-microscopic level for evidence of gold deposition. Using photochemical and hydrogen peroxide staining methods on histological sections perivascular accumulations of gold were detected in the hypothalamus 4 hr after gold-thioglucose injection, but they were negative on tissue from mice injected with bipiperidyl mustard. Gold could not be detected ultrastructurally in the early lesion in the hypothalamus of mice injected with goldthioglucose but it was evident in the macrophages of the 3-month glial scar as coarse and fine electron-dense spicules. Similar spicules were not seen in mice injected with bipiperidyl mustard.

Sex differences in hyperphagia and body weight gains following goldthioglucose-induced hypothalamic lesions in mice

Hypothalamic damage was induced in age-matched male and female albino mice by goldthioglucose injection, and their food consumption and body weight were compared over the following 60-day period. Sex differences in food consumption were also investigated as a function of palatability of food. Results show no significant sex differences in food consumption, although marked sex differences in body weight gain were noted. Female mice with hypothalamic damage gained more body weight than did male mice with hypothalamic damage. These results suggest that obesity induced by hypothalamic damage is probably due to the combined effects of neural and hormonal changes.

Sex differences in body weight following gonadectomy and goldthioglucose injections in mice

Following gonadectomy, male mice of a C57 Black strain show decreased weight gains and females show increased weight gains relative to intact controls. A similar sex difference results from a single injection of goldthioglucose, and after 100 days, female mice overtake the weight gains of the males. It is suggested that these differences are in part due to the drug causing a functional gonadectomy. This is discussed in the light of experiments on the interaction between gonadectomy and goldthioglucose.

Early vascular changes in the brain of the mouse after injections of goldthioglucose and bipiperidyl mustard.

Early vascular changes in the brain of the mouse after injections of goldthioglucose and bipiperidyl mustard.

Effects of gold thioglucose and bipiperidyl mustard on pituitary prolactin and growth hormone content of C3H mice.

SummaryThe effects of a single injection of gold thioglucose (GTG) and bipiperidyl mustard (BM) on the pituitary prolaction and GH contents of C3H mice were studied. Virtually all mice receiving the drugs became obese in 8 weeks. GTG and BM increased pituitary prolactin concentration 37 and 24% at 4 weeks and 42 and 40%, respectively, at 8 weeks (p<0.01). GH concentration was enhanced significantly (30%; p<0.01) only by BM treatment at 8 weeks, BM increased the weights of the pituitary glands, adrenals, ovaries, and the uteri; whereas only the uterine weights were increased by GTG treatment. The data suggest that prolactin and/or GH may be related to the induction of obesity by GTG and BM.

Comparison of Goldthioglucose and Monosodium Glutamateinduced Lesions In the Hypothalamus of Mice

The compound goldthioglucose (GTG) has been shown to produce lesions in the ventromedial region of hypothalamus in mice. Also, lesions in the same region of hypothalamus have been reported after single parenteral administration of monosodium glutamate (MSG). This study has examined the development of these lesions over time with the electron microscope.Mice were given single intraperitoneal injections of either GTG (either 0.2 or 0.6 mg/g body wt) or MSG (either 4.0 or 6.0 mg/g body wt). Animals injected with GTG were killed at times varying between 1 hr - 14 days post injection while those injected with MSG were killed between 3 hours and 3 days after injection. Hypothalamic lesions that developed 3 hours after MSG injection involved only glia cells (Fig. 1) immediately lateral to the base of the third ventricle in the accuate nucleus.

Comparative Goldthioglucose Effects on Goats, Sheep, Dogs, Rats, and Mice

Goldthioglucose injections produce lesions in the ventromedial area of the hypothalamus readily in mice and in some cases in rats. These lesions usually result in hyperphagia and obesity. Glucose and insulin solutions were injected into jugular veins of goats and sheep for an hour to increase glucose utilization rate which in mice increases the severity of the hypothalamic lesion. Immediately folowing this, goldthioglucose and insulin were injected into a carotid artery for 30 minutes while the opposite carotid was occluded. This treatment caused high levels of goldthioglucose in the brain. Even though the gold concentration of the venous blood was 30 to 40 times that of mice which developed hypothalamic lesions, the goats and sheep did not develop hypothalamic lesions. Dogs similarly treated or rats injected intravenously with goldthioglucose also did not have hypothalamic lesions. Mice injected intraperitoneally first with glucose and insulin for 1hour and then goldthioglucose and insulin for 30 minutes had hypothalamic lesions. Sheep suffered some impairment of liver function and severe kidney dysfunction which was often lethal. The ruminants were sensitive to the toxic effects of goldthioglucose but resistant to any hypothalamic-lesioning effect.

The Effects of Gold Thioglucose and Monosodium Glutamate on Growth and Feed Consumption of the Chicken and the Japanese Quail

A single intraperitoneal injection of gold thioglucose to the chicken (Gallus domesticus) and the Japanese quail (Cotrunix cotrunix japonica) showed that the LD 50 of the drug was 0.25mg/g body weight for White Leghorn 12-day-old cockerels, 0.1mg/g for the adult male quail and more than 0.1mg/g for the adult female quail.Neither growth promotion nor increase in feed consumption was observed in the cockerel and the quail which received the LD 50 dose of gold thioglucose, as compared with the cockerel and quail which did not receive the drug. No hyperphagia or obesity was observed in the gold thioglucose-treated-chicken and quail.No damage to the ventromedial nucleus in hypothalamus was observed in the gold thioglucose-treated-cockerels (Courtesy to the inspection by Dr. Shigeto Kanematsu, Iwate University, Morioka-shi).Subcutaneous injections of monosodium glutamate at the dosage level of 0.5, 1 and 2mg/g body weight for 10 days to the 3-day-old quail of both sexes did not induce any accerelation of growth or increase in feed consumption as compared with the nontreated control birds.

Hypothalamic blood flow following goldthioglucose-induced lesions

Blood flow to the ventromedial region of hypothalamus was studied in mice at various times following injection of the chemical compound goldthioglucose (GTG). India ink solution was used to outline the blood vessels. It was found that blood flow to the hypothalamus was not effected up to 4 hours after GTG injection. At 5 hours after injection, notable blood flow changes were observed in the region of the infundibulum, while from 6 hours to 21 days (the latter being the longest postinjection period studied), blood flow was reduced to the entire ventromedial hypothalamic region. This area extended from the anterior hypothalamic region to the mamillary nucleus and included the arcuate and ventromedial nuclei. No reduction in blood flow was observed in the lateral hypothalamic region. Also, blood vessels, occasionally outlined within the region of the lesion, showed normal-appearing cells immediately adjacent to them.

The Effect of Gold Thioglucose on Food Consumption and Reproduction of the Japanese Quail (Coturnix coturnix japonica)

GOLD thioglucose (GTG) has been used to destroy selectively the ventromedial nucleus of the hypothalamus of mice (Deter and Liebelt, 1964; Liebelt and Perry, 1957, 1967; Marshall et al., 1955) and of some strains of rats (Wagner and de Groot, 1963; Talbert and Hamilton, 1954). The main effects which have been noted in mice after injection of GTG and subsequent damage to the ventromedial nucleus have been: hyperphagia, obesity (see Deter and Liebelt, 1964; and Liebelt and Perry, 1967; for review), interference with the estrous cycle (Browning and Kwan, 1964) and development of the mammary glands (Browning and Kwan, 1964; Browning et al., 1965/66).The specificity of gold thioglucose in comparison to other gold compounds with respect to the induction of hyperphagia and obesity has been established by Mayer and Marshall (1956).To our knowledge no investigations on the effect of GTG on the food consumption and reproduction of Japanese…

Behaviour Changes in Cba Mice as a Result of One Goldthioglucose Injection

AbstractOne intraperitoneal injection of goldthioglucose may produce in mice very specific brain lesions followed by a period of hyperphagia leading to obesity. The question is raised whether or not the brain lesions affect feeding behaviour only or that besides this changes in non-feeding behaviour may also contribute to the hyperphagia and obesity observed. Feeding of solitary mice was recorded automatically during 24 h periods after o, 12 and 24 hours of food deprivation and after the GTG treatment. It was found that after GTG injection the mice temporarily (dynamic hyperphagic phase) behave very much like intact hungry ones in that they 1) eat large amounts of food a day 2) gnaw off a bit of food rapidly 3) show little non-feeding behaviour during a meal 4) ingest much food per meal. This period is followed by a static phase during which food intake is somewhat above normal, while the animals show again about normal feeding patterns. Direct observation of the behaviour of solitary mice showed the following: 1) The tendency to sleep has increased permanently and is not related to the occurring obesity. 2) The tendency to climb and to explore the cage has decreased permanently. 3) During a meal non-feeding behaviour occurs rarely. 4) The tendency to groom is not affected. 5) Some (perhaps all) behaviours are less stabile now, as is indicated by the increased occurrence of interruptions. Social behaviour of GTG treated males has been changed drastically as was established by direct observation. It was found that these males, whether or not obese, only rarely fight with other males and that they have a very low tendency to mate. They show a high tendency to flee but on the other hand they often approach the partner although in a very cautious way. However, it was also found that hungry GTG treated mice may fight for their food. This complex change in behaviour patterns of GTG treated mice is discussed briefly and it is concluded that, a. probably the behaviour changes observed are the result of a number of independent effects of the brain lesions, b. the hyperphagia and resulting obesity can be explained largely by a specific lesion in satiety areas of the brain, c. the phenomenon of finickiness, as described by other authors, in the obese animals may be the result of changes in non-feeding behaviour, d. the extreme hunger drive of the dynamic hyperphagic animals may mask signs of finickiness and even enable them to fight for their food, although their aggressiveness in other respects has decreased markedly.

Electron microscopic observations of early changes in the ventromedial hypothalamus of the mouse following goldthioglucose.

The lesion of the ventromedial region of the mouse hypothalamus which results from a single parenteral injection of goldthioglucose, has been studied at both light3,7,12,15.,18,27) and electron microscope levels13). There is evidence from distribution studies following injection of labeled goldthioglucose23), and neutron activation of sections of the hypothalamus of mice treated with the unlabeled compound4,5) which indicates that the drug enters the neural compartment rapidly. Existing studies13) with the electron microscope following goldthioglucose administration are limited to 12‐and 96‐hour post‐injection intervals. The present experiments were undertaken to ascertain the ultrastrctural changes evident in the ventromedial nucleus of the hypothalamus at closely spaced time intervals during the first 24 hours after treatment with the compound.

Some metabolic aspects of the obese-hyperglycemic syndrome in mice.

Some aspects of the metabolism of obesehyperglycemic mice are presented in the light of recent observations on the Swedish colony of these animals. A screening procedure has been elaborated, which allows early detection of those growing mice that will later develop the obese-hyperglycemic syndrome. The observation that intraperitoneal glucose injections induce a higher frequency of glucosuria in those suckling mice which are homozygous for the obese-hyperglycemic gene furthermore suggests that the impairment of the glucose metabolism represents a primary lesion in these animals. The obese-hyperglycemic syndrome is associated with a reduced endocrine activity of the testis. Quantitative microscopic analyses of the testis, both from obese-hyperglycemic mice kept on a restricted food intake and from mice in which hyperphagia and obesity had been induced by injections of gold thioglucose, revealed that other factors than overeating and/or obesity are responsible for the depression of the testis function. An increased activity ofβ-glucuronidase has been reported in serum and arteries from inviduals with diabetes or severe arteriosclerosis. However, among the various tissues analysed in the obese-hyperglycemic mice only the adrenals displayed a significantly higherβ-glucuronidase activity than the lean litter mates. Studies of the enzymatic dehydrogenation of isocitrate revealed considerably higher ratios between the NADP+- and NAD+-specific enzyme activities in the skeletal muscle and liver from the obese-hyperglycemic mice. The observation that the liver dehydrogenation of isocitrate was more dependent on NADP+ in the latter animals must not necessarily be attributed to the presence of a hyperlipogenesis, since similar ratios were recorded for the NADP+- and NAD+-linked isocitric dehydrogenase activities when the adipose tissue from the obese-hyperglycemic mice was compared with that from the lean sibling controls.

Body Protein and Fat, Blood Glucose and Free Fatty Acids in Various Strains of Mice

AbstractCarcass composition was determined in the NMRI, CBA, Swisse and DBA strains, and in NMRI X Swisse made obese by injection of goldthioglucose. Fasting for 24 hrs resulted in different degrees of weight loss depending on the strain. At the same time analysis of carcass composition revealed strain differences with regard to protein and fat. The changes of glucose and FFA in plasma after 24 hrs without food also varied among the strains.

The influence of overeating on the endocrine testis function in mice

The obese-hyperglycemic syndrome in mice is associated with a reduced endocrine activity of the testis. The hypothesis that the presence of obesity inhibits the gonadotrophin secretion with a resulting hypoplasia of the Leydig cells was tested by quantitative microscopic analyses both of obese-hyperglycemic mice kept on a restricted food intake and in mice in which hyperphagia and obesity had been induced by injections of gold-thioglucose. There was no evidence for the view that overeating in itself gives rise to any depression of the endocrine testis function in mice.

THE EFFECT OF HYPERGLYCEMIA ON HYPOTHALAMIC GOLD UPTAKE AND HYPERPHAGIA IN GOLDTHIOGLUCOSE-TREATED MICE.

The accumulation of gold in the hypothalamus and the development of hyperphagia and obesity were studied in mice given a single intravenous injection of goldthioglucose at various levels of blood glucose concentration. It was found that the glucose concentration prevailing at the time of goldthioglucose injection was correlated directly with the level of free and bound goldthioglucose in the blood 3 minutes later, with the hypothalamic uptake of gold, with the extent of the hypothalamic lesion, and with the severity of the subsequent hyperphagia and obesity. Hyperglycemia was associated with an increased gold deposition throughout the brain. A gold content of 88 +/- 12 microg/mg wet tissue in the hypothalamus of fasted animals was associated with clearcut lesions in all animals studied, whereas a similar gold content in the control brain lobes of hyperglycemic animals was not associated with lesions in any animal. This finding indicates that some regions in the brain (e.g. the ventral hypothalamus) are more susceptible than others to damage by goldthioglucose.

PROGRESSIVE HYPERGLYCAEMIA IN EXPERIMENTAL OBESITY OF ALBINO RATS.

THE coincidence of two hereditary metabolic disorders, diabetes and obesity1,2, is quite common although their interrelationship is still a matter of speculation as there is no proof that obesity causes diabetes. On the other hand, the importance of various physiological conditions, such as obesity, puberty or pregnancy, in precipitating diabetes cannot be overlooked. Few experimental observations record their coincidence. Mayer et al.3 showed the connexion between obesity and diabetes in an obese-hyperglycaemic strain of mice. Long4 mentioned that only with great difficulty was a temporary diabetes-like state induced in hypothalamic obesity in albino rats by partial pancreatectomy. Except for the observation of Katsuki et al.5, who induced obesity and hyperglycaemia by gold thioglucose injection in intact mice, there is no recorded evidence that in intact animals hyperglycaemia results from obesity. While investigating the metabolic character of obese albino rats, we had already noticed that the fasting blood sugar was significantly high in these animals in comparison to control animals6.

Effect of goldthioglucose injections on survival, organ damage and obesity in the rat.

SummaryPreliminary studies showed that weanling Long-Evans rats are less susceptible to goldthioglucose than are adults; the LD50 for 50 g animals was 0.25 mg/g. Some adult Sprague-Dawley rats were found to withstand doses of GTG that were lethal to adult Long-Evans rats, and to demonstrate a developing obesity. More severe VMH lesions were seen in female than in male rats following GTG injection. Glial damage without neuronal destruction appeared in several GTG-injected rats. Treatment with phlorhizin and BAL reduced renal damage produced by GTG injection. GTG injection, in adult rats, produced a triphasic blood-glucose pattern.

Coenzyme A and acetylation in various experimental obesities.

Coenzyme A concentration and in vivo acetylation of sulfanilamide were determined in genetically obese-hyperglycemic mice, their lean littermates, littermates made obese by injection of gold thioglucose, yellow-obese mice, and Swiss mice. Metabolically obese mice show an increased total liver and kidney coenzyme A content. Rates of acetylation differ from one type to the other as does the effect of fasting on this parameter. These observations are discussed in the light of data on lipogenesis and cholesterogenesis previously obtained in these animals.