Search PubMed⌕ Search

Biomedical subjects

A C Sullivan

Publications and source records attributed to A C Sullivan.

16 recordsLinked to original sources
PubMed1979

Carbohydrate metabolism in lean and obese Zucker rats.

Carbohydrate metabolism was evaluated in lean and obese Zucker rats. Plasma glucose concentration, renal and hepatic gluconeogenesis, and hepatic glycogen content and rates of synthesis were investigated in 2-mo and 8-mo-old animals. Mild hyperglycemia was observed in obese Zucker rats compared to lean rats and was more pronounced in males than in females. Rates of glucose disappearance were normal in both female and male rats, although there was a trend toward decreased clearance in the male. Total organ hepatic and kidney PEPCK activity and kidney glucose production were elevated in obese compared to lean rats. Total organ hepatic glycogen levels and rates of glycogen synthesis were increased significantly in obese compared to lean, the increase being greater in males than females. The mild hyperglycemia present in obese Zucker rats is not associated with delayed disappearance of intravenously administered glucose, but may be due to the increased production of glucose by whole kidney and liver.

Aging↗
PubMed1978

Caloric compensatory responses to diets containing either nonabsorbable carbohydrate or lipid by obese and lean Zucker rats.

The effects on food intake and body weight in lean and obese Zucker rats were evaluated following substitution in the diet with either 1) poorly absorbable lipid (hydrogenated soybean oil) for corn oil, or 2) nonabsorbable carbohydrate (fiber) for glucose. Lean Zucker rats compensated for the reduced caloric availability of the high-fiber and hydrogenated oil diets by increasing food consumption. In contrast, obese rats did not respond significantly to these dietary alterations and failed to attain caloric balance during the 16-day study. These differences in caloric compensatory responses were reflected in body weight gains. There were no differences in the amount of weight gained by lean rats fed either the high-or low-fiber diets because of compensatory hyperphagia in the high-fiber group. Lean rats fed the hydrogented oil diets gained less weight than controls fed corn oil diets, even in the presence of compensatory hyperphagia, because of the enhanced fecal excretion of water and metabolites caused by the poorly absorbed fat diet. As a result of a delayed and incomplete response to reduced caloric availability, obese rats fed the high-fiber and hydrogenated oil diets gained significantly less weight than the obese rats fed low-fiber and corn oil diets.

Animals↗
PubMed1978

Comparative effects of saturated and unsaturated lipids on hepatic lipogenesis and cholesterogenesis in vivo in the meal-fed rat.

The effects of saturated and unsaturated lipids on in vivo rates of hepatic lipogenesis and cholesterogenesis were compared. Lipogenic and cholesterogenic rates were determined in meal-fed rats either after feeding 1%, 5%, 10%, or 20% dietary corn oil or hydrogenated soybean oil for 14 days, or after intrgastric administration of fatty acyl ethyl esters (18:0, 18:1, or 18:2) for 1 and 3 days. Dietary hydrogenated soybean oil was not absorbed, whereas dietary corn oil and the intragastrically administered fatty acyl ethyl esters were well absorbed. Fatty acid synthesis measured from 3H2O and [14C] alanine was inversely correlated with unsaturated dietary fat content, but was unchanged by saturated dietary fat. A single daily administration of 18:0, 18:1, or 18:2 was ineffective in altering lipogenic rates. However, fatty acid synthesis was decreased by three consecutive daily doses of 18:1 or 18:2 (5 g/kg), but not by 18:0. Hepatic rates of cholesterogenesis from 3H2O and [14C] alanine were markedly enhanced by the administration of 10% or 20% saturated dietary fat. Feeding 1%, 5%, or 10% corn oil diets did not have an effect on cholesterogenesis. The 20% corn oil diet reduced the rate of conversion of [14C]anine into cholesterol while the rate of conversion of 3H2O remained unchanged. Neither the 1 day not 3 day oral administration of 18:0 or 18:1 had any effect on cholesterol synthesis; thereas the administration of 18:2 increased the conversion of [14C] alanine into cholesterol by 30% but did not after the rates of cholesterogenesis from 3H2O. These data suggest the following: a) fatty acid synthesis responds selectively to 18:0, 18:1, and 18:2; b) the inhibition of fatty acid synthesis by unsaturated fatty acids is time dependent; c) the rate of fatty acid synthesis is inversely proportional to the concentration of unsaturated dietary fat; d) prolonged feeding with a completely saturated diet will increase fecal fat excretion and hepatic cholesterol synthesis; and e) the regulation of fatty acid synthesis by dietary lipid is independent of the regulation of cholesterol synthesis.

Animals↗
PubMed1978

Pharmacological treatment of obesity.

Obesity results when the ingestion of energy exceeds its utilization, leading to an excessive expansion of the adipose tissue mass. Current pharmacological therapy for the obese patient focuses primarily on reducing energy intake. Anorectic agents reduce food consumption by modifying central systems in the brain which are involved in appetite regulation. These agents are reviewed in terms of mechanism of action, and clinical safety and efficacy in suppressing appetite and promoting weight loss. Newer anorectic agents which are being evaluated currently in clinical and animal studies are described. Clinical assessments of therapeutic regimens utilizing the thyroid hormones and human chorionic gonadotropin are evaluated. Finally, an overview of novel pharmacological approaches to the treatment of obesity is presented.

Appetite Depressants↗
PubMed1977

Reactivity and inhibitor potential of hydroxycitrate isomers with citrate synthase, citrate lyase, and ATP citrate lyase.

The four isomers of hydroxycitrate have been tested as substrates and inhibitors for citrate synthase, citrate lyase, and ATP citrate lyase. None of the isomers served as a substrate for citrate synthase and they were moderate to weak inhibitors of this reaction. Of the four isomers, only (pncit)-(2S)-2-hydroxycitrate did not serve as a substrate for citrate lyase while (pncit)-(4S)-4-hydroxycitrate was the only isomer which did not serve as a substrate for ATP citrate lyase. No consistent pattern of reactivity or inhibitor potency was seen with the different isomeric hydroxycitrates. It is proposed that more than one mode of binding is possible between the isomers and the three different active sites.

ATP Citrate (pro-S)-Lyase↗
PubMed1977

Hupolipidemic activity of (--)-hydroxycitrate.

The influence of (--)-hydroxycitrate, a potent competitive inhibitor of adenosine triphosphate (ATP) citrate lyase, on serum triglyceride and cholesterol levels, and in vitro and in vivo rates of hepatic fatty acid and chloesterol synthesis was investigated in normal and hyperlipidemic rat model systems. (--)-Hydroxycitrate reduced equivalently the biosynthesis of triglycerides, phospholipids, cholesterol, diglycerides, cholesteryl esters, and free fatty acids in isolated liver cells. In vivo hepatic rates of fatty acid and cholesterol synthesis determined in meal-fed normolipidemic rats were suppressed significantly by the oral administration of (--)-hydroxycitrate for 6 hr, when control animals exhibited maximal rates of lipid synthesis; serum triglyceride and cholesterol levels were significantly reduced by (--)-hydroxycitrate. In two hypertriglyceridemic models-the genetically obese Zucker rat and the fructose-treated rat-elevated triglyceride levels were due, in part, to enhance hepatic rates of fatty acid synthesis. (--)-Hydroxycitrate significantly reduced the hypertriglyceridemia and hyperlipogensisi in both models. the marked hypertriglyceridemia exhibited by the triton-treated rat was only minimally due to increased hepatic lipogenesis;(--)-hydroxycitrate significantly inhibited both serum triglyceride levels and lipogenesis in this model.

Animals↗
PubMed1977

Comparative effects of (--)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo.

(--)-Hydroxycitrate and (+)-allo-hydroxycitrate were investigated for their effects on lipid synthesis in vivo under conditions of either high carbohydrate feeding or 24 hr fasting. Changes in rates of lipid synthesis resulting from the oral administration of these compounds were monitored with the use of radiolabeled H2O, alanine, and acetate. In the fed rat, (--)-hydroxycitrate significantly reduced the incorporation of H2O and alanine into fatty acids and cholesterol. An increased incorporation of labeled H2O into fatty acids but no change in cholesterol synthesis in the fasted rat suggested that (--)-hydroxycitrate may be an activator of acetyl CoA carboxylase. With (--)-hydroxycitrate administration, acetate incorporation into fatty acids and cholesterol was subject to pool dilution effects under fed or fasted states. (+)-allo-Hydroxycitrate was ineffective in modulating the rates of fatty acid synthesis under either nutritional condition. Both (--)-hydroxycitrate and (+)-allo-hydroxycitrate were shown to be in vitro activators of acetyl CoA carboxylase, the former being a much stronger activator than the latter. Thus, stereospecificity of the hydroxycitrate isomers was demonstrated in both the inhibition of lipid synthesis (previously shown to occur at adenosine triphosphate citrate lyase) and the stimulation of fatty acid synthesis (possibly occurring at acetyl CoA carboxylase).

Acetyl-CoA Carboxylase↗
PubMed1977

(-)-Hydroxycitrate and conditioned aversions.

The capacity of various salts of (-)-hydroxycitrate to produce conditioned rejection of a 0.25% saccharin solution was evaluated. The ethylenediamine salt of (-)-hydroxycitrate produced strong conditioned rejection of saccharin under both deprivation and nondeprivation conditions, but this effect was less than produced by equimolar doses of lithium chloride. The sodium salt of hydroxycitrate produced no conditioned rejection of saccharin in water deprived rats but did so in nondeprived animals. In these experiments, food intake was reduced by (-)-hydroxycitrate only during the first hour following administration of the drug. The magnitude of appetite rejection did not correspond to the degree of conditioned rejection, lending support to the conclusion that the food intake reduction was not merely a consequence of aversive effects of the drug.

Animals↗
PubMed1977

Insulin and glucagon: plasma levels and pancreatic release in the genetically obese Zucker rat.

Circulating levels of insulin and glucagon, as well as their release from isolated pancreatic islets, have been measured in Zucker rats to examine the effect of genotype, sex and diet. The obese animals had higher plasma insulin levels and enhanced release from islets when compared to lean controls. Conversely, obese animals, despite no significant differences in fed plasma levels of glucagon, showed substantially reduced release from islets. Diet had no main effect on any of these parameters.

Animals↗
PubMed1977

Metabolic regulation as a control for lipid disorders. II. Influence of (--)-hydroxycitrate on genetically and experimentally induced hypertriglyceridemia in the rat.

These studies were designed to determine whether genetically and experimentally induced hypertriglyceridemia were correlated with hyperlipogenesis, and whether inhibiting fatty acid synthesis would reduce serum triglyceride levels. Hypertrigylceridemia, resulting from genetic obesity in Zucker rats and fructose feeding or Triton administration to Charles River rats, was examined in relation to in vivo rates of heatic fatty acid synthesis, and the influence of (--)-hydroxycitrate (a potent competitive inhibitor of ATP citrate lyase) on serum triglyceride levels and lipogenesis was determined. Zucker obese rats demonstrated significantly increased rates of fatty acid synthesis and levels of serum triglycerides compared to their lean litter mates; lipogenic rates and circulating triglycerides were reduced markedly by the oral administration of (--)-hydroxycitrate. Fructose administered in the diet or drinking water induced a hypertriglyceridemia which was associated with a marked increase in hepatic lipogenesis, and (--)-hydroxycitrate reduced significantly both parameters. In contrast to the significant role that increased rates of lipogenesis apparently played in the development of hypertriglyceridemia in the Zucker rat and fructose-fed rat, Triton given intravenously produced a marked rise in serum triglycerides which could not be accounted for, to an appreciate extent, by increased rates of fatty acid synthesis. (--)-Hydroxycitrate reduced serum triglyceride levels and hepatic lipogenic rates equivalently in the Triton-treated and nontreated rats.

ATP Citrate (pro-S)-Lyase↗