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Biomedical subjects

A Sclafani

Publications and source records attributed to A Sclafani.

At least 127 records · Page 7Linked to original sources

Effects of hypothalamic knife cuts on feeding induced by paraventricular norepinephrine injections.

The relationship between the fiber systems involved in the hypothalamic noradrenergic feeding response and the medial hypothalamic (MH) hyperphagia syndrome was appraised in male rats using knife cuts. Parasagittal knife cuts in the perifornical hypothalamus produced hyperphagia and excessive weight gain but failed to disrupt feeding in response to paraventricular hypothalamic injections of norepinephrine (NE). Coronal knife cuts in the posterior hypothalamus which extended from the midline to the lateral perifornical region also failed to disrupt NE feeding. These findings indicate that the output of the noradrenergic feeding system does not follow the feeding pathway implicated in the MH hyperphagia syndrome. They also suggest that the output of the noradrenergic feeding system is not directed laterally beyond the level of the fornix nor caudally into the lower brainstem over the medial forebrain bundle.

Animals↗

The dopaminergic mediation of a sweet reward in normal and VMH hyperphagic rats.

The role of dopamine in mediating the rewarding quality of a sweet saccharin-glucose (SG) solution was investigated by comparing the effects of the dopamine receptor blocker pimozide, the bitter adulterant quinine, and solution dilution on the consummatory response to the solution in normal and VMH rats. Experiments 1 and 2 demonstrated that pimozide and quinine caused a dose/concentration dependent dependent reduction in the intake of and the licking response to a SG solution. Pimozide treatment caused an equivalent suppression in the intake of the normal and VMH rats, in both the dynamic and static phases, whereas quinine adulteration caused a greater suppression in the intake of the VMH rats. The effects of pimozide and quinine on initial lick rate were also different. Experiment 3 demonstrated that dilution of a SG solution produced a concentration related decrease in intake and licking response. Dilution of the SG solution, like pimozide treatment, affected the intake of the normal and VMH rats in an equivalent manner. The effects of solution dilution and pimozide treatment on the licking response were also similar. The results suggest that the mechanisms by which pimozide and quinine reduce the hedonic quality of natural rewards are functionally dissimilar. The similarity between pimozide treatment and solution dilution suggests that pimozide reduces the positive affective quality of natural reinforcers. The results are discussed in terms of the dopamine theory of reward, the role of dopamine in hypothalamic hyperphagia, and VMH finickiness.

Animals↗

The effects of ileal transposition on food intake and body weight loss in VMH-obese rats.

Rats were made obese by VMH knife-cuts and then a 5 or 10 cm segment of terminal ileum was transposed to the duodenum. After surgery, the food moved from the stomach into upper duodenum and then traveled through the transposed ileal segment to lower duodenum and continued down the remaining normal digestive tract. Ileal transposition caused a significant reduction in food intake and a substantial loss of body weight. There was no difference in weight loss with 5 and 10 cm ileal transpositions in obese rats, but weight loss was much less in lean rats. Weight loss was accompanied by a considerable loss in dissectable body fat and an increase in the actual weight of the pancreas and small intestine. These changes are probably caused by the unusual stimulation of a short segment of terminal ileum with undigested food and pancreatic enzymes and may have been mediated by the release of ileal hormones. Changes in plasma levels of metabolites, intracellular enzymes, and protein are presented and the importance of this surgery for the treatment of human obesity is evaluated.

Alkaline Phosphatase↗

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↗

Zucker fafa rats maintain their obese body composition ten months after jejunoileal bypass surgery.

In order to evaluate the long-term effects of intestinal bypass surgery in an animal model of early onset hypercellular-hypertrophic obesity, adult female obese and lean Zucker rats were given jejunoileal bypass surgery or sham operations. At sacrifice ten months post-surgery, body weights of obese bypass rats were nearly reduced to lean bypass levels. This reduction in body weight was not accompanied by normalization of body composition or of the hyperinsulinemia and hypertriglyceridemia characteristic of this obese syndrome. Obese bypass rats maintained 44 percent of their weight as lipid compared to 12 percent in lean bypass rats and 15 percent in sham-operated lean rats. In addition, obese bypass rats maintained elevated adipose tissue lipoprotein lipase activity and increased fat cell size and were hyperinsulinemic and hypertriglyceridemic. Furthermore, obese bypass rats had reduced carcass protein and reduced weight and DNA and/or protein contents in heart, liver, muscle and kidney. Therefore, although bypass surgery resulted in significant weight loss, it did not normalize the obese syndrome and may result in serious reductions in the weight and cellularity of vital organs.

Adipose Tissue↗

The effects of pimozide on the consumption of a palatable saccharin-glucose solution in the rat.

Two experiments investigated the role of dopamine in reward mechanisms by examining the effects of the specific dopamine receptor blocker pimozide on drinking behavior in the rat. In Experiment 1, the effects of pimozide on the consumption of a palatable saccharin-glucose solution were compared to the effects of quinine adulteration of the same solution. Pimozide and quinine both reduced 30 min/day consumption, decreased lick rate early in the drinking session and reduced lick efficiency in a dose related manner. In Experiment 2, the effects of pimozide on the consumption of a saccharin-glucose solution and water were compared in thirsty and nonthirsty rats. Pimozide suppressed the consumption of both water and the saccharin-glucose solution in a dose related manner. However, saccharin-glucose solution intake was suppressed more than water intake, and this effect was independent of thirst drive. The drug also decreased lick rate early in the drinking session and lick efficiency. The results are discussed in terms of the reward and sensory-motor deficits produced by dopamine receptor blocking agents.

Animals↗

Influence of diet palatability on noradrenergic feeding response in the rat.

Adult male rats which displayed a reliable feeding response to intrahypothalamic injections of norepinephrine (NE) on a chow diet were subsequently tested on one of three diets: an unpalatable quinine-adulterated meal, a palatable fat-adulterated meal, or a "neutral" unadulterated meal. The quinine diet completely blocked the NE feeding response, while the fat diet produced a small and unreliable reduction in the feeding response. When food deprived all groups increased their food intake, although the fat diet group tended to overeat, and the quinine diet group tended to undereat relative to the unadulterated diet group. The failure of the palatable fat diet to potentiate the NE feeding response does not support the hypothesis that this response mimics the ventromedial hypothalamic hyperphagia syndrome. The blocking effect of the quinine diet on NE feeding is consistent with other evidence which suggests that NE mediated the eating behavior induced by glucoprivation.

Animals↗

Atropine fails to block the overconsumption of sugar solutions by hypothalamic hyperphagic rats.

Adult female rats given bilateral parasagittal knife cuts in the medial hypothalamus (VMH group) were hyperphagic and became obese on a chow diet, compared with sham-operated controls. The VMH rats also overconsumed, relative to controls, sucrose and glucose solutions during 30 min/day tests. Pretreating the VMH and control rats with atropine methyl nitrate (1.0, 5.0, or 10.0 mg/kg) reduced their intake of the sugar solutions in three out of five experiments, and in all experiments it suppressed their 24-hr chow intake. However, the VMH rats continued to drink more of the sugar solutions than did the controls after all atropine treatments, and in three out of four experiments their hyperphagia on the chow diet was not blocked by the atropine. The results do not support the hypothesis that vagally stimulated insulin release or other cholinergically mediated cephalic responses of digestion are essential for the expression of hypothalamic hyperphagia and finickiness.

Animals↗

Vagotomy blocks hypothalamic hyperphagia in rats on a chow diet and sucrose solution, but not on a palatable mixed diet.

Adult female rats were given ventromedial hypothalamic parasagittal knife cuts (VMH treatment) or control surgery (Con treatment), followed 10 days later by subdiaphragmatic vagotomy (Vag treatment) or sham vagotomy (Sham treatment). The hyperphagia and obesity produced by the VMH cuts to rats on a chow diet was completely blocked by vagotomy (VMH-Vag group). Vagotomy also inhibited the VMH rats' overconsumption of a 20% sucrose solution during 1 hr/day and 24 hr/day tests, which contrasts with the effects of atropine treatment. However, when offered a selection of palatable foods (cookies, sweet milk, high-fat ration) in addition to chow, the VMH-Vag rats overate and gained considerably more weight than did the Con-Vag rats or the Con-Sham rats. The Con-Vag rats, on the other hand, gained less weight than did the Con-Sham rats on the palatable diet. The results indicate that intact subdiaphragmatic vagi are not essential for the expression of VMH hyperphagia and finickiness, and they therefore question the role of vagally mediated cephalic responses in the hypothalamic hyperphagia syndrome. On the other hand, the results indicate that in brain-intact animals vagotomy suppresses the development of diet-induced obesity.

Animals↗

The role of hyperinsulinema and the vagus nerve in hypothalamic hyperphagia reexamined.

Three series of experiments investigated the role of hyperinsulinemia and the vagus nerve in the hyperphagia and obesity syndrome produced in female rats by knife cuts in the ventromedial hypothalamus (VMH). The findings of the first series revealed that VMH cuts do not produce hyperinsulinemia when the rats are prevented from overeating, but insulin levels are elevated in rats allowed to overeat. The second series of experiments demonstrated that VMH-cut rats overconsume sweet sugar solutions during daily short-term tests, and that pharmacological blockade of vagal efferent activity with atropine methyl nitrate fails to inhibit this overconsumption. The third study revealed that subdiaphragmatic vagotomy completely blocks VMH hyperphagia and obesity on a chow diet, but does not prevent overeating and rapid weight gain in rats fed an assortment of highly palatable food. These findings indicate that vagally mediated insulin release is not an essential component to the VMH knife cut syndrome.

Animals↗

Appetitive behavior after jejunoileal bypass.

There is now extensive evidence that jejunioleal bypass (JIB) surgery reduces food intake in obese patients, and that in most cases this is the primary cause of their postoperative weight loss. Associated with the reduced food consumption are other behavioral changes, including alterations in meal patterns, appetite ratings, taste responsiveness, and food-related attitudes. Experimental animal research indicates that JIB surgery also reduces food intake in obese rats and alters their feeding patterns. The hypophagia and weight loss produced by the surgery in rats is dependent upon both the degree and type of obesity. The exact mechanism(s) by which JIB surgery suppresses food intake remains to be determined, although recent animal research implicates both visceral malaise and overstimulation of the lower ileum as contributing factors.

Animals↗

Control of body weight by lower gut signals.

The importance of the terminal ileum in the control of food intake and body weight was studied in rats made obese by VMH knife cuts and in lean controls. In the first study, 35 rats had either jejunoileal bypass, antibiotic infusion into the bypassed segment, resection of the bypassed segment of sham operation. All three experimental treatments reduced food intake and produced large and statistically equivalent weight losses compared to the sham surgery control. Apparently, physiological signals or bacterial toxins arising in the bypassed segment are not essential to the loss of body weight. In the second study, 38 rats had either 5 or 10 cm segments of the terminal ileum transposed to mid-duodenum or upper jejunum or served as surgical controls. As in the previous study, the experimental rats reduced their food intake and sustained a substantial loss of body weight. Stimulation of the terminal ileum with nutrient-rich chyme was sufficient to cause most of the weight loss seen after jejunoileal bypass.

Animals↗

Intestinal bypass surgery produces conditioned taste aversion in rats.

Intestinal bypass surgery reduced the body weight of obese humans and rats primarily by decreasing food consumption. The present study reports that jejunoileal bypass surgery in rats produces a strong and persistent conditioned taste aversion to a novel-flavored solution with which it is paired. This finding indicates that the jejunioleal bypass produces a long-lasting malaise, which may be an important factor in the anorexia and weight loss produced by the operation.

Animals↗