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Biomedical subjects

A C Sullivan

Publications and source records attributed to A C Sullivan.

At least 73 records · Page 4Linked to original sources
PubMed1982

Sympathetic activity in thyroid-treated Zucker rats.

Treatment of lean and obese 3- to 4-mo-old male Zucker rats with 0.03% thyroid powder (TP) for up to 41 days produced a decreased weight gain and carcass lipid content in obese but not lean rats, without reduction in food intake. Improved thermogenesis in TP-treated obese rats was evidenced by increased basal rectal temperatures and improved cold tolerance, although TP did not alter the lower stress-evoked levels of plasma norepinephrine (NE) or epinephrine of the obese rats. Levels of NE and/or NE turnover were lower in hearts, aortas, pancreata, interscapular brown adipose, and epididymal white adipose pads of obese compared with lean rats. Both NE levels and turnover were increased in the hearts and aortas of TP-treated obese rats, suggesting increased sympathetic activity in these organs. Basal but not stress-evoked hyperglycemia, hyperinsulinemia, and hyperglycerolemia in the obese rats were partly or totally corrected by TP treatment as was defective in vivo utilization of fatty acids. Therefore 0.03% TP administration had a selective effect on the obese Zucker rat compared with the lean and led to decreased weight gain associated with improved thermogenesis. These effects appeared to be related in part to increased sympathetic function in some organs and improved utilization of fatty acids.

Animals↗
PubMed1982

Neuroendocrine interrelationships in major depressive disorder.

The authors administered the thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) to 54 patients who met DSM-III criteria for major depressive disorder and to 19 nondepressed patients. A blunted thyrotropin (TSH) response to TRH injection was noted in 18 depressed patients (33%) but in no nondepressed patients. An escape from dexamethasone suppression was noted in 23 depressed patients (43%) but in only 2 nondepressed patients (11%). The combined sensitivity of the DST and the TRH test in identifying major depressive disorder was 67% with 92% specificity. Only 6 depressed patients (11%) had abnormal responses to both the DST and the TRH test, suggesting that the hypothalamic-pituitary-adrenal axis dysregulation and hypothalamic-pituitary-thyroid axis dysregulation are independent phenomena. These findings support the combined use of these neuroendocrine tests in clinical practice.

Adolescent↗
PubMed1981

Defective catecholamine metabolism in peripheral organs of genetically obese Zucker rats.

Catecholamine (CA) metabolism in peripheral organs of lean and obese, 3-4 and 7-8 month (mo) old male Zucker rats was studied to define further the known abnormalities of peripheral sympatho-adrenal functions in the obese rat. Norepinephrine (NE) levels in all sympathetically innervated organs from obese rats (aorta, heart, pancreas, brown adipose tissue and white adipose tissue) were decreased to 9-55% of those in lean rats at 3-4 mo. NE turnover, measured by inhibition of tyrosine hydroxylase (TH) with a-methyl-p-tyrosine, was also decreased in these same organs. NE levels and turnover were also decreased (by 50-95%) in many, but not all organs assayed of 7-8 mo old obese rats, while there were inconsistent changes in organ dopamine and epinephrine levels at both ages. Decreased NE metabolism was associated with decreased dopamine-beta-hydroxylase (D beta H) activity in every organ assayed from obese rats at 3-4 mo and 7-8 mo of age except in the superior cervical ganglia of 7-8 mo old rats. There were no consistent changes in TH or phenylethanolamine-N-methyltransferase activities. In 3-4 mo old obese rats, decreased D beta H activity was associated with decreased immunoprecipitable enzyme protein in the hearts but not in the adrenal glands, where differences in the affinity for substrate appeared to explain the activity differences. These results suggest that the previously reported defect in stress-induced plasma NE levels in obese rats could be explained by decreased D beta H activity in nerve terminals of their sympathetic nervous system and that, in this case, D beta H may play an important role in the regulation of NE synthesis.

Adipose Tissue↗
PubMed1981

Fatty acid and cholesterol synthesis from specifically labeled leucine by isolated rat hepatocytes.

Hepatocytes isolated from female rats meal-fed a high-glucose diet were incubated in Krebs-Henseleit bicarbonate medium containing 16.5 mM glucose, 3H2O, and 14C-labeled amino acids (-)-Hydroxycitrate depressed the incorporation of 3H2O and [14C] alanine into fatty acids and cholesterol. Incorporation of [U-14C]leucine into lipids was not affected but incorporation of 3H2O into lipids was decreased significantly by (-)-hydroxycitrate. (-)-Hydroxycitrate depressed the incorporation of radioactivity from [2-14C]leucine into fatty acids and cholesterol by 61 and 38%, respectively, and stimulated the incorporation of radioactivity from [4,5-3H]leucine 35 and 28%. As [2-14C]leucine labels the acetyl-CoA pool and [4,5-3H]leucine labels the acetoacetate pool, it was concluded that mitochondrial 3-hydroxy-3-methylglutaryl-CoA is not incorporated intact into cholesterol, and that acetoacetate can be activated effectively in the liver cytosol for support of cholesterol and fatty acid synthesis.

Acetoacetates↗
PubMed1981

Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats.

Fatty acid synthesis and CO2 production were evaluated in hepatocytes from lean and obese Zucker rats in the presence of 3H2O, and several carbon precursors. The incorporation of 3H2O into fatty acids was greater in obese compared to lean rats in both the isolated hepatocyte and in vivo. The rates of incorporation of 3H2O into fatty acids and cholesterol in hepatocytes of both lean and obese rats were linear for 2 hr, in the absence or presence of 16.7 mM glucose. Rates of fatty acid synthesis were higher in the presence of 16.7 mM glucose compared to the absence of glucose in both lean and obese while rates of cholesterol synthesis were similar. The incorporation of 3H2O into fatty acids, but not into cholesterol, was correlated with increasing glucose concentration and was 2 to three-fold higher in hepatocytes of obese compared to lean rats in the presence of several carbon precursors. Differences in CO2 production between lean and obese rats suggested increased pentose phosphate shunt activity, decreased pyruvate dehydrogenase activity, and lower tricarboxylic acid cycle activity in obese rats. Fatty acid synthesis and CO2 production from 3H2O and [U-14C]glucose in hepatocytes of lean and obese rats was similarly elevated by insulin and depressed by glucagon at several concentrations, suggesting that hepatocytes of obese animals respond to these hormones. These data indicate that rates of hepatic fatty acid synthesis although higher in obese rats respond to modulation in a fashion which is similar to the response in lean rats. The present studies suggest that the oxidation of several carbon precursors in the tricarboxylic acid cycle is diminished in obese compared to lean rats, but pentose phosphate shunt activity is greater in the obese Zucker rats.

Animals↗
PubMed1981

(--)-threo-Chlorocitric acid: a novel anorectic agent.

A new class of peripherally acting anorectics is described in these studies. The four stereoisomers of chlorocitric acid which are structurally similar to the known anorectic, (--)-threo-hydroxycitric acid, all suppressed food intake when administered at high doses to rats. Only one of these isomers, (--)-threo-chlorocitric acid, retained its anorectic activity at lower doses. The anorectic potency of (--)-threo-chlorocitric acid was approximately 40-fold greater in dogs than in lean and obese rats. The decreased food intake in rats resulted in a significant reduction of body lipid, without affecting protein levels. In contrast to the tolerance which was observed with the continued administration of mazindol or diethylpropion, tolerance to the anorectic effect of (--)-threo-chlorocitric acid did not develop. These studies suggest that (--)-threo-chlorocitric acid might be useful as an antiobesity agent.

Animals↗
PubMed1981

Studies on the mechanism of action of a novel anorectic agent, (--)-threo-chlorocitric acid.

(--)-threo-Chlorocitric acid, a novel and potent anorectic agent in rats and dogs, decreased food intake to a comparable extent in rats fed chow, low fat, or high fat diets. This inhibition of food intake was not the result of conditioned aversion. Unlike (--)-threo-hydroxycitric acid, a structurally related compound which inhibits fatty acid synthesis, (--)-threo-chlorocitric acid did not suppress fatty acid synthesis in an isolated hepatocyte system or in vivo. (--)-threo-Chlorocitric acid significantly delayed the rate of gastric emptying. Of the four stereoisomers of chlorocitric acid, (--)-threo-chlorocitric acid was the most active both in delaying gastric emptying and producing anorexia in rats. It is suggested that the mechanism by which (--)-threo-chlorocitric acid may suppress food intake is through a reduction of gastric emptying.

Animals↗
PubMed1981

Metabolic and sympatho-adrenal abnormalities in the obese Zucker rat: effect of chronic phenoxybenzamine treatment.

The obese Zucker rat manifests a number of physiologic and metabolic abnormalities which are controlled or modulated by the sympatho-adrenal system. The interrelationship of these was examined by subjecting 3-4 month old male, homozygous lean and obese Zucker rats to various stresses which are known to activate the sympatho-adrenal system, and by chronic (16-19 days) phenoxybenzamine (PBZ) treatment to block alpha-adrenergic receptors. Both obese and lean PBZ treated rats gained only 1% and 10% of the body weight of their respective control rats during the treatment period, while only the lean rats had a significant reduction (20%) in food intake. Control obese rats failed to maintain rectal temperature after 4 hr at 7 degrees C and their relative output of plasma catecholamines (CA) to cold stress, as measured from indwelling atrial cannulae, was decreased. PBZ treatment did not alter this rectal temperature response although it was associated with increased baseline norepinephrine levels (at ambient temperature 21-22 degrees C) and relative output of CA in the obese rats, suggesting tat sympathetic neural activity was increased under these circumstances. No abnormalities of sympatho-adrenal function, as reflected in plasma CA levels, were found in treated or control obese rats immobilization for 1 hr followed by decapitation. Simultaneously obtained baseline plasma glucose levels were similar in untreated lean and obese rats, but insulin and glycerol levels in the obese rat were 1350% and 213% of lean values, respectively. During sequential stresses, the obese rats became markedly hyperglycemic and hyperglycerolemic compared to the lean rats, while insulin levels were decreased more in the obese than lean rats (12-15% versus 34-35% of controls, respectively). PBZ affected insulin levels only in the obese rats, reducing their baseline levels by 4-fold and stressed induced levels to those seen in the lean control rats. These results suggest that some of the metabolic and physiologic abnormalities of the obese Zucker rat which are modulated by the sympatho-adrenal system can be normalized by procedures which increase sympatho-adrenal activity.

Animals↗
PubMed1981

Effect of (-)-hydroxycitrate on development of obesity in the Zucker obese rat.

Young Zucker lean (Fa/-) and obese (fa/fa) female rats were fed the fatty acid synthesis inhibitor (-)-hydroxy-citrate as a dietary admixture for 39 days. In the lean rats, (-)-hydroxycitrate treatment decreased body weight, food intake, percent of body fat, and fat cell size. In the obese rat, food intake and body weight were reduced but the percent of body fat remained unchanged. Throughout the treatment period, obese rats maintained a fat cell size equivalent to their obese controls. Although a reduction in fat cell number in the obese rats occurred during the treatment period, marked hyperplasia was observed during the posttreatment period. The results of this study indicate that the obese rat, despite a substantial reduction in body weight produced by (-)-hydroxycitrate, still defends its obese body composition.

Adipose Tissue↗
PubMed1980

Metabolic consequences of fasting in old lean and obese Zucker rats.

The effects of fasting on lipid and carbohydrate metabolism and plasma insulin and glucagon levels were compared in lean and obese Zucker rats. Sixteen-month-old female and male rats were fasted for periods of 2, 4, 6 and 12 days. Fasting produced significant decreases in hepatic rates of lipid, cholesterol, and glycogen synthesis, as well as circulating levels of triglycerides, cholesterol, phospholipids, and insulin. Significant increases in hepatic lipid levels and serum free fatty acids were noted. When compared to lean rats, obese rats had elevated rates of hepatic lipid and glycogen synthesis, hepatic lipid and glycogen stores, serum triglycerides, cholesterol, phospholipids, and plasma insulin. Lean rats had higher plasma glucagon levels. Sex differences in several parameters were observed. Females demonstrated higher levels of lipid and cholesterol synthesis and serum free fatty acids, whereas serum cholesterol levels and hepatic glycogen stores were higher in males. Following a 12-day fast, carcass fat and protein content were decreased in both lean and obese rats, but the obese animals maintained an obese body composition. It is concluded that fasting results in qualitatively similar metabolic and hormonal changes in both lean and obese rats, but that abnormalities in carbohydrate and lipid metabolism persist in obese rats even after a 12-day fast.

Animals↗
PubMed1980

Abnormal sympatho- adrenal function and plasma catecholamines in obese Zucker rats.

The functional integrity of the peripheral sympathetic nervous system and adrenal medulla was assessed in homozygous, lean and obese, 7--8 month old male Zucker rats by the changes in plasma catecholamines during cold and immobilization stresses. Five of eight obese, but no lean rats died during a 24 hr cold stress (4--7 degrees C) from hypothermia. While both lean and obese rats had decreased rectal temperatures after 4 hr of cold stress, the obese had lower temperatures, relatively less of an increase of plasma norepinephrine (NE) and epinephrine (E) than the lean rats, and were unable to consistently maintain their temperatures even during intravenous NE infusions. Obese rats had lower rectal temperatures and higher plasma NE and dopamine levels at 21--22 degrees C ambient temperature, a relative failure to increase plasma NE and E levels after 1 hr of immobilization, but normal or supranormal plasma catecholamine levels after decapitation compared to the lean rats. These results suggest that the obese Zucker rat has abnormalities of both peripheral sympatho-adrenal function and thermoregulation, which may play roles in the development and/or maintenance of many of the physiological and metabolic defects in this animal model of genetic obesity.

Adrenal Glands↗
PubMed1980

An experimental model for assessing effects of anorectics on spontaneous food intake of obese subjects.

Ad libitum access to food by use of a platter service is a new method for studying spontaneous food intake in obese human subjects. The effect of diethylpropion on energy intake was evaluated by the platter-service method in 2 overweight adult male subjects hospitalized on a metabolic unit for 41 days. This double-blind experiment was divided into 12 consecutive 3-day study periods during each of which the subjects received either 25 mg diethylpropion or a matching placebo before each meal. In this design protocol the 12 study periods provided 6 consecutive drug-placebo trials for each subject. To encourage ad libitum ingestion, food was served "family style" from large platters and pitchers at meals, and snacks were always available. Subjects were not aware that their intake was being monitored. On diethylpropion administration both subjects had an average decrease in energy intake of 11% and 15% (p less than 0.005). The platter service model, which provides a near-natural eating situation under systematic control, appears to be a useful and sensitive method for assessing effects of anorectic drugs on spontaneous food intake.

Adult↗
PubMed1980

Antiobesity activity of pluronic L-101.

Pluronic L-101, a hydrophobic surface-active agent, was a potent in-vitro inhibitor of human pancreatic lipase. When administered as a 1 percent or 3 percent dietary admix to meal-fed rats, pluronic L-101 produced a significant and dose-dependent decrease in body-weight gain while not affecting food consumption. Excretion of dietary fat in the feces was enhanced significantly in a dose-dependent manner during pluronic L-101 treatment. Pluronic F-68, a hydrophilic surface-active agent which was a poor in-vitro inhibitor of human pancreatic lipase, did not produce decreases in body-weight gain or increase fecal-fat excretion in rats. The decreased body-weight gain produced by pluronic L-101 was reflected in a decreased percentage of carcass fat; the percentage of carcass protein was unchanged. Liver wet weight was reduced significantly only at the 3 percent pluronic L-101 level. Serum levels of cholesterol, triglyceride and glucose remained unchanged. During pluronic L-101 treatment no overt signs of toxicity were observed.

Absorption↗