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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 343 records · Page 19Linked to original sources

Opiate receptors, food intake and obesity.

The present studies tested the effect of acute and chronic administration of naloxone on food intake of lean and genetically obese (ob/ob) mice. Acute administration of naloxone, a drug which blocks opiate receptors, produced a greater reduction of food intake in obese (ob/ob) mice than in the lean littermates. For chronic experiments with naloxone, the daily feeding period was shortened to eight hours and two injections of naloxone were given four hours apart. With this procedure of scheduled-feeding the food intake of both lean and obese mice was depressed during the first hour after injecting naloxone. However, beginning on the second day of treatment, the lean mice began to eat more food than the untreated controls during the eight hour feeding period. Food consumption by lean mice reached values 140 to 200% above the control levels between the fourth and sixth day. In the obese mice the rise in food intake was more gradual and did not reach 200% of the control value until the sixth day. Body weight changes reflected the changes in food intake. In contrast to naloxone, chronic treatment with morphine lowered food intake and blocked the stimulatory effect of naloxone. Our findings suggest that endogenous opioids may play a role in signalling satiety and in regulating long-term energy balance.

Animals↗

Obesity in Osborne-Mendel and S 5B/Pl rats: effects of sucrose solutions, castration, and treatment with estradiol or insulin.

S 5B/Pl rats were tested for their susceptibility to develop obesity when 1) ovariectomized, 2) given injections of insulin, and 3) given a sucrose solution to drink instead of water. The results obtained in Osborne-Mendel rats susceptible to dietary obesity when fed a high-fat diet were compared to those obtained in the S 5B/Pl rats not susceptible to dietary obesity. When tested at the end of 10 wk, ovariectomized rats of both strains had gained 22% more weight than sham-operated controls. Replacement estradiol injections suppressed food intake in both strains with a concomitant loss in body weight. Osborne-Mendel rats tolerated at least 40 U of U-100 protamine zinc insulin/day and rapidly gained weight whereas S 5B/Pl rats given more than 2 U U-100 protamine zinc insulin/day died. Compared to female Osborne-Mendel rats drinking water, rats drinking a sucrose solution accumulated more body fat and had higher levels of serum immunoreactive insulin and lower levels of serum free fatty acids. The substitution of a sucrose solution for plain drinking water suppressed weight gain in S 5B/Pl rats.

Animals↗

Obesity-inducing hypothalamic knife cuts: effects on lipolysis and blood insulin levels.

The effect of two experimental manipulations designed to mobilize lipids from adipose tissue have been investigated in rats with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Those animals which displayed hyperphagia during the initial 5 days VMH knife cuts were then restricted in food intake to reduce body weights to levels comparable to that of the sham-operated controls. Two weeks following the knife-cut lesions, or sham operations, animals in the first experiment were exposed to the cold for 60 min, and those in the second experiment were injected with 2-deoxy-D-glucose (2-DG). The injections of 2-DG increased the level of glycerol in the control animals but not in the animals with VMH knife cuts. Both groups showed a rise in glucose. Plasma insulin and triglycerides were the same in both groups. Exposure to the cold increased the level of glycerol in both groups. The insulin levels were lower in the corresponding groups with knife cuts. These studies show that VMH knife cuts do not produce hyperinsulinemia in pair-gained rats.

Animals↗

Salivary gland weight and nerve growth factor in the genetically obese (ob/ob) mouse.

The salivary glands of genetically obese male mice are significantly smaller than those of lean male mice, but the salivary glands of female mice do not differ in weight. The increases in weight of salivary glands in male mice after treatment with T3 at 50, 150, or 500 ng/day or with several doses of isoproterenol were comparable on a percentage basis, but the weights in the ob/ob mice were always smaller than any of those in the lean mice. Measurements of nerve growth factor (NGF) in several tissues showed a significantly lower concentration in the salivary glands of obese female mice than in same tissue from female lean mice. There were no differences in NGF levels in brown fat or in the cortex, cerebellum, or brain stem. The concentration of epidermal growth factor, in contrast to that of NGF, was not lower in the salivary glands of obese mice. Testosterone increased the weight of the salivary glands, spleen, and kidney in obese female mice, but the weight of the salivary glands in lean animals remained significantly higher than that in the obese mice both with and without treatment. Testosterone significantly increased the NGF concentration in salivary glands, but the values in treated male mice were only one tenth those in the treated lean animals.

Animals↗

Adrenergic modulation of glucagon and insulin secretion in obese and lean humans.

The adrenergic modulation of immunoreactive insulin (IRI) and glucagon (IRG) secretion was studied in 5 massively obese subjects hospitalized ion a metabolic ward. Epinephrine was infused alone or in combination with propranolol, a beta adrenergic blocking drug, or with phentolamine, an alpha adrenergic blocking drug. Epinephrine infusion produced a significant (p less than .02) rise in IRG levels which was blocked by addition of either phentolamine or propranolol. Pure alpha adrenergic stimulation with propranolol-epinephrine infusion inhibited IRG secretion (p less than .02). IRI levels decreased with propranolol-epinephrine infusion (p less than .02), increased with phentolamine-epinephrine infusion, and were not affected by infusion of epinephrine alone. Glucose concentrations rose with all 3 infusions but were less with phentolamine-epinephrine. A control group of 4 lean outpatients on a ad lib diet demonstrated a similar pattern but the changes of IRG secretion were smaller than in the obese subjects and were not statistically significant. We conclude that in obese humans IRI secretion is increased by beta adrenergic stimulation, is decreased by alpha adrenergic stimulation, and is unaffected by combined alpha and beta adrenergic stimulation. In contrast, IRG secretion is stimulated by combined alpha and beta adrenergic stimulation, is inhibited by pure alpha adrenergic stimulation, and is unaffected by pure beta adrenergic stimulation.

Adult↗

Effects of thyroid hormone and adrenalectomy on [Na+ + K+]ATPase in the ob/ob mouse.

The absence of the thyroid stimulation of hepatic [Na+ + K+]ATPase in obese (ob/ob) mice has been investigated. A wide range of tri-iodothyronine (T3) concentrations failed to enhance the hepatic [Na+ + K+]ATPase of ob/ob mice made hypothyroid by methimazole treatment but glycerophosphate dehydrogenase activity was maximally stimulated at low doses of T3. Adrenalectomy increased the basal activity of [Na+ + K+]ATPase to levels found in lean control mice and restored the response of this enzyme to T3. Body weight gain was unaffected by the induction of hypothyroidism in either lean or ob/ob mice. It is concluded that the adrenal steroids play an important role in the expression of [Na+ + K+]ATPase activity in the ob/ob mouse.

Adrenalectomy↗

Lipoprotein lipase activity in adipose tissue from obese human beings.

The activity of lipoprotein lipase (LPL) released from human adipose tissue was measured before and after an oral glucose load in obese (n = 8) and normal (n = 7) weight subjects. The enzymatic activity of LPL release from fat tissue by heparin rose significantly one hour after glucose in the normal subjects. There was no such rise in LPL in adipose tissue from obese subjects. Serum triglyceride, insulin and glycerol were higher in the obese than in the lean subjects.

Adipose Tissue↗

Hypothalamic obesity. The autonomic hypothesis and the lateral hypothalamus.

Several lines of evidence support the hypothesis that derangements in the function of the autonomic nervous system play an important role in the development of hypothalamic obesity. Vagotomy below the diaphragm, reverses the syndrome. In diabetic rats cured of their diabetes with transplants of fetal pancreatic tissue beneath the renal capsule, ventromedial hypothalamic (VMH) lesions do not produce the characteristic rise in food intake nor do they significantly increase serum insulin. These observations indicate that the hyperinsulinaemia following VMH lesions is the result of neural connections rather than from a circulating humoral factor released following VMH injury. The smaller salivary glands, reduced level of glucagon and impaired mobilization of fatty acids during stress in VMH lesioned rats point to reduced activity of the sympathetic nervous system. The impaired mobilization of fat from retroperitoneal depots in VMH lesioned rats during fasting is similar to the effect of sympathetic denervation of the retroperitoneal fat pad. Similarly, unilateral sympathectomy caused an increased weight gain in rats almost as much as unilateral VMH lesions but significantly less than in bilaterally lesioned rats. These studies with fasting and feeding implicate the VMH in the control of the sympathetic nervous system. When atropine and epinephrine were given to VMH lesioned rats, there was a significant depression in basal and glucose-stimulated levels of insulin. Finally when VMH lesions were placed after lateral hypothalamic lesions, the effect of the VMH lesions did not seem to be reduced, suggesting that the two effects are independent. A model dealing with the effects of VMH lesions is presented in an attempt to integrate these findings.

Animals↗

Evidence for a circulating ergostatic factor: studies on parabiotic rats.

The effect of electrolytic ventromedial hypothalamic lesions or forced overfeeding through gastric cannulas was studied in parabiotic rats. In one experiment a ventromedial hypothalamic lesion in one member of the parabiotic union was associated with an increased fatness in the lesioned rat and a decrease in fat pad weight and a rise in body density (loss of fat) of the unlesioned animal. In the other two experiments a high fat or high carbohydrate diet was tube fed to one member of a parabiotic union. The average preinfusion intake per rat was 56 kcal/day. When 90 kcal/day were given through the intragastric cannula, oral intake of calories for the two animals fell to approximately 44 kcal/day. Body fat of the non-tube-fed animal was less than in the tube-fed controls. These studies suggest the presence of an ergostatic (energy stabilizing) factor that enters and is transported in the blood with passage from one animal to another.

Adipose Tissue↗

Physiological control of energy balance.

Physiological control of energy balance is reviewed in terms of food seeking and enery (food) intake, utilization and storage. In particular the role of hormonal and metabolic signals, as clarified by whole-body calorimetry and cellular studies, and the interaction of energy expenditure with the mechanism regulating intake are outlined.

Adolescent↗

Weight gain of rats fed medium-chain triglycerides is less than rats fed long-chain triglycerides.

Weight gain was measured in rats fed test diets with two types of fat: corn oil and medium-chain triglycerides (MCT). These diets were selected because fatty acids from corn oil enter the circulation as chylomicrons through the lacteals. Fatty acids from medium-chain triglycerides reach the liver directly through the portal circulation. Weight gain was normal when the diet contained MCT, but was increased with the higher percentage of corn oil in the diet. Caloric intake was lowered, but its conversion to fat was higher on the high-fat diets. Serum triglycerides, but not glucose, were higher in both male and female rats fed the MCT compared to the corn-oil diet. These experiments suggest that the route by which nutrients are absorbed plays a role in regulating body-fat storage.

Absorption↗