Effects Of Ventromedial Hypothalamic Lesions Research Articles

Effects of ventromedial hypothalamic lesions on circadian rhythms in serum insulin, glucose, triglyceride and food intake in rats.

The effects of ventromedial hypothalamic (VMH) lesions on the circadian periodicity of serum insulin, glucose, triglyceride and food intake were studied in rats. The rhythms of serum insulin, glucose and triglyceride did not persist in VMH lesioned rats. The glucose level during the light period was reduced. The triglyceride and insulin levels were elevated. The VMH lesions markedly increased food intake during the later half part of the light cycle but kept it significantly less during the first half part. Thus, the VMH lesions abolished the circadian rhythmicity of serum insulin, glucose and triglyceride and attenuated the rhythmicity of eating through increase in daytime consumption.

Pre- and postabsorptive insulin secretion in chronic decerebrate rats.

Basal, taste-stimulated (preabsorptive), and postabsorptive insulin secretion and plasma glucose responses were studied in chronic decerebrate rats and their pair-fed neurologically intact controls. In experiment 1, preabsorptive insulin responses (PIR) elicited by oral infusions of glucose solution was measured in chronic decerebrate rats. Oral glucose was ingested and led to a significant short-latency elevation in plasma insulin levels. Plasma glucose levels remained constant during this time. These data show that caudal brain stem mechanisms, in isolation of the forebrain, are sufficient for the neurally mediated PIR elicited by oral glucose stimulation. In experiment 2, effects of decerebration on postabsorptive insulin secretion were measured. During the 3 h immediately after transection there was no effect of decerebration on peripheral plasma insulin or glucose levels. Thereafter, however, basal plasma insulin levels of decerebrate rats were at least twice that of control rats. Plasma glucose levels of both groups remained identical despite the hyperinsulinemia in decerebrate rats. Atropine treatment decreased, and phentolamine administration elicited a greater absolute and percent change increase in insulin levels of decerebrate rats. These data indicate that altered autonomic tone contributes to maintaining the basal hyperinsulinemia in the decerebrate rat. In response to intragastric meals and glucose and intravenous glucose administration, insulin secretion was greater in decerebrate than in control rats. Percent change in insulin levels from base line was similar in both groups after intragastric meals and intravenous glucose. In response to intragastric glucose, however, percent increase in insulin levels was greater in decerebrate rats. Decerebrate rats demonstrated mild glucose intolerance after intragastric and intravenous treatments. These results are contrasted with the known effects of ventromedial hypothalamic lesions on insulin secretion and glucose homeostasis.

Changes in body weight and food-related behaviour induced by destruction of the ventral or dorsal noradrenergic bundle in the rat

Three experiments contrasted the effects of 6-hydroxydopamine-induced lesions of the ventral noradrenergic and dorsal noradrenergic projections, predominantly to hypothalamus and cortex, respectively, upon body weight changes and food-related behaviour in the rat. In general, ventral noradrenergic bundle lesions enhanced weight gain and these effects were exaggerated by the provision of palatable cheese to the standard chow diet. In contrast, lesions of the dorsal noradrenergic bundle produced minor changes in body weight. Associated with the effects of ventral noradrenergic bundle lesions were hyperphagia, enhanced suppression of intake of food adulterated with quinine, (at high concentration), a small attenuation of food neophobia, and enhanced acquisition, but not performance, of the eating response to tail-pinch stimulation. These ventral noradrenergic bundle lesions failed to alter basal activity levels, amphetamine anorexia or the diurnal pattern of eating or activity. In contrast, lesions of the dorsal noradrenergic bundle did not produce either hyperphagia or enhanced rejection of food adulterated with quinine. However, there was a strong attenuation of food neophobia and a retarded acquisition (but unimpaired performance) of eating in response to tail-pinch stimulation. The results are discussed in connection with previous studies of ventral and dorsal noradrenergic bundle lesions, with the effects of ventromedial hypothalamic lesions and with the underlying behavioural and physiological processes that mediate these contrasting effects of different neuroanatomical patterns of central noradrenaline depletion.

The significance of hyperphagia and diet composition on the metabolism in ventromedial hypothalamic lesioned male rats.

The metabolic consequences of ventromedial hypothalamic lesion were studied in a group of aged male rats which were obese and had decreased response to insulin. The effects of hyperphagia and ventromedial hypothalamic lesion per se were separated by comparing experimental animals fed isocalorically with controls and animals fed ad libitum. Ventromedial hypothalamic lesion as such led to increases in the glucose conversion to fatty acid and in lipoprotein lipase activity in adipose tissue. Protein catabolism as reflected by plasma urea levels, was enhanced. The lipoprotein lipase activity in heart tended to be lower after VMH lesion. These metabolic changes were amplified in the VMH lesioned rats fed ad libitum. The liver glycogen content was lowered by VMH lesion, but this effect was abolished by hyperphagia. In parallel experiments the influence of diet composition was studied by feeding similar groups with diet of high fat content. The glucose incorporation in fatty acids was in all groups markedly and similarly inhibited by the high fat diet. The increase in lipoprotein lipase activity in heart and adipose tissue of control rats with high fat intake could not be demonstrated in any of the groups with ventromedial hypothalamic lesion. The plasma urea level in the control group was not affected by the diet, but tended to increase in the ventromedial hypothalamic lesioned groups on high fat intake. These findings demonstrate that the well known metabolic effects of ventromedial hypothalamic lesions are also manifest in obese insulin resistant male rats. Furthermore, the responses to changes in diet composition are different from those of the control rats.

Effects of guanethidine sympathectomy on ventromedial hypothalamic obesity.

Since ventromedial hypothalamic (VMH) lesions apparently produce chronic increases in parasympathetic activity and decreases in sympathetic responses, two experiments were performed to determine whether decreases in sympathetic tone alone are sufficient either to produce elements of the VMH syndrome or to potentiate the expression of the syndrome in animals with lesions. In experiment 1, rats that had been injected with guanethidine sulfate for 5 wk (40 mg X kg-1 X day-1) to produce a permanent sympathectomy (SympX) were maintained on a high-fat diet and subsequently subjected to VMH lesions. In experiment 2, adrenal-demedullated animals were treated with guanethidine for 6 wk and then subsequently underwent VMH lesions. SympX in the studies (81 and 85% depletion of superior cervical ganglia neurons, respectively) did duplicate the effects of VMH lesions on salivary gland weights. In neither experiment, however, did SympX alone or in combination with demedullation mimic the effects of VMH lesions on food intake, body weight, or body fat. Determinations of free fatty acids (FFAs) in the experiments confirmed that VMH lesions elevate basal FFA levels, but they also indicated that effective VMH lesions need not impair the FFA mobilization to 2-deoxyglucose challenges as some basomedial hypothalamic lesions do. In addition, experiment 2, which employed a prolonged period of high-fat feeding, revealed that SympX plus adrenal demedullation could potentiate (a 13% increase) the effects of VMH lesions on body weight. The results taken together do not support the conclusion that a preponderance of the VMH syndrome can be accounted for by the type of reduction in sympathetic tone produced by guanethidine.

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.

Effects of ventromedial hypothalamic lesions on adipose tissue of weanling male rats.

In weanling male rats, destruction of the ventromedial hypothalamus causes increased carcass lipid deposition and decreased linear growth without changes in food intake or blood glucose levels. These changes are not dependent on altered pituitary function. Lipogenesis and glucose utilization are increased in vivo and in vitro, while gluconeogenesis is accelerated in vivo. The enhanced lipogenesis occurs before increased gluconeogenesis.

Effect of ventromedial hypothalamic lesions on the secretion of somatostatin, insulin, and glucagon by the perfused rat pancreas

Somatostatin, insulin, and glucagon secretion by the perfused pancreas were studied in adult female rats 10 days after ventromedial hypothalamic (VMH) lesions and in sham operated controls to assess the role of their hypothalamic control. Insulin secretion was significantly greater in VMH-lesioned rats both under basal conditions and after stimulation by theophylline and arginine plus theophylline. Basal glucagon secretion was greater in VMH-lesioned rats as was the glucagon response to theophylline alone and in combination with arginine. Basal somatostatin secretion was similar in VMH and control rats but somatostatin secretion induced by theophylline and by arginine plus theophylline was significantly increased in VMH-lesioned rats. Both the pancreatic content and concentration of somatostatin were increased in VMH-lesioned rats. These results indicate the presence of hyperresponsiveness of A, B, and D cells following VMH destruction and provide new evidence for a role of the hypothalamus in the regulation of pancreatic somatostatin secretion.

Ventromedial hypothalamic lesions elevate basal and cephalic phase gastric acid output

With the use of a new technique for the measurement of gastric acid output in the rat, this study identifies ventromedial hypothalamic (VMH) lesion-induced changes in gastric acid secretion. Basal and cephalic phase gastric acid secretion were monitored in VMH- and sham-lesioned control rats on days 1, 5, 9, 13, and 17 postlesion as well as after the full development of obesity. VMH lesions resulted in increases of both phases of secretion. The magnitude of hypersecretion in lesioned rats developed with time and was fully developed by day 9 postlesion. The hypersecretion did not require a hyperphagia or weight gain, but its degree correlated with subsequent weight gain. These data, in conjunction with a review of VMH lesion effects on insulin secretion, suggest a widespread effect of VMH lesions on visceral secretory responses. The relevance of these data to the etiology of the VMH syndrome is discussed.

Effects of VMH lesions on schedule induced and schedule dependent behaviors

Ten male hooded rats were exposed to an FI 1 min food reinforcement generator schedule at 80% body weight and schedule dependent lever pressing and schedule induced licking and drinking were recorded. When lever pressing, licking, and drinking stabilized the 10 rats were divided into two groups. One group was composed of 4 animals subjected to sham lesion procedures plus one animal with asymmetrical ventromedial hypothalamic (VMH) lesions. The other group was composed of 5 animals with bilateral symmetrical VMH destruction. Results demonstrate that VMH destruction produces a slight transient decrease only in water intake when on schedule at 80% body weight. When animals are returned to ad lib eating and body weight increased and they are returned to the test chamber, the VMH lesion animals display increased licking and drinking. Although VMH lesion animals ate and drank more than controls, they did not eat more in response to food deprivation and did not drink more in response to water deprivation and the intraperitoneal administration of hypertonic saline. The presence or absence of food or water was the determining factor in the overeating or excessive drinking of the VMH lesion animals. Results are discussed in terms of gastrointestinal influences on the hypothalamic mechanisms involved in the production of schedule induced behaviors.

Ventromedial hypothalamic lesions and the mobilization of fatty acids.

We have explored the effects of ventromedial hypothalamic lesions on the mobilization of free fatty acids in rats exposed to several stresses. The rise in free fatty acids and glycerol in response to norepinephrine had the same time-course and dose-response characteristics in the sham-operated and lesioned animals, indicating comparable degrees of peripheral responsiveness to this hormone. Forced swimming significantly lowered insulin and increased glycerol and free fatty acids more in control than in ventromedial hypothalamic-lesioned rats. During fasting, the rise in glycerol and free fatty acids was smaller in the lesioned rats, but the fall in insulin was greater. Exposure to cold raised fatty acids and glycerol more in the control than in the sham-operated animals, but had no significant effect on plasma insulin or glucose concentration. Injection of 2-deoxyglucose was done on lesioned or control rats with intact or removed adrenal medullas. The rise in free fatty acids and glycerol was less in the lesioned rats than in the controls, and was not affected by adrenodemedullation. The rise in glucose, however, was completely blocked in the adrenodemedullated rats. Changes in insulin were small and not statistically significant. The reduced mobilization of fatty acids from adipose tissue depots after ventromedial hypothalamic injury is consistent with the hypothesis that the ventromedial hypothalamic region serves to modulate activation of the sympathetic nervous system.

Some effects of ventromedial hypothalamic lesions, adrenalectomies, and corticosterone replacement therapy on energy expenditure in rats

The present study tested the hypothesis that the decreases in energy expenditure reported following ventromedial hypothalamic (VMH) lesions in rats are a function of the decreases in adrenal function. Five groups of rats received 21 1hr/day sessions in activity wheels and then were subjected to either VMH lesions, adrenalectomies, the respective sham-operations, or no operation. Following surgery, each rat was again given access to an activity wheel for 24 1-hr test sessions. During the test phase the rats received a sequence of drug/no drug conditions which consisted of: (1) no injection; (2) injections of the vehicle substance; or (3) injections of corticosterone in the vehicle substance. Under the no-drug conditions, running levels of the VMH-lesioned and adrenalectomized rats decreased, with the levels of VMH-lesioned rats being more severely depressed. Corticosterone replacement therapy reinstated the activity levels of the adrenalectomized rats, but not those of the VMH rats. The hypothesis that the reductions in activity following adrenalectomy or destruction of the VMH are due to disruption of the same mechanism was not supported.

Effects of ventromedial hypothalamic lesions on rat ethanol intake

The consumption of food, water and ethanol solutions, in free choice condition, was studied in 9 rats with electrolitic lesion of ventromedial hypothalamus, before and after the operation and compared with 2 controls submitted to sham operation. Changes in body weight were studied between 20 and 30 days after the operation. In all the experimental rats there was an increase in food, water consumption and body weight while ethanol intake decreased significantly.

The effect of ventromedial hypothalamic lesions on metabolism and insulin secretion in rats on a controlled feeding regimen.

The metabolic effect of ventromedial hypothalamic (VMH) lesions, which are known to cause hyperphagia and obesity, has been studied in rats kept on a controlled light and food regimen. The animals were sacrificed at 4 different times during the second postoperative day. A feeding-induced hypersecretion of insulin was found to the VMH-lesioned animals. It was accompanied by a marked hypoglycemia as compared to the control groups during the feeding period. The glycogen content of liver and diaphragm in the lesioned groups is increased as compared to the controls during the same period. The VMH-lesioned animals showed hypertriglyceridemia both in the fed and fasted state, whereas the postabsorptive plasma levels of free fatty acids and glycerol were decreased. An increased level of urea was observed in all lesioned groups. This is in accordance with the demonstrated protein catabolism which follows VMH lesions.

Effects of ventromedial hypothalamic lesions on spontaneous intraspecies aggression in male rats

Bilateral lesions in the ventromedial hypothalamic area of male rats are reported to increase the occurrence of spontaneous intraspecies aggression. The results are discussed in terms of the relationships between intraspecies aggression, fear acquisition, and reaction to novel environments.

Effect of ventromedial hypothalamic lesions on schedule-induced polydipsia

Rats with bilateral electrolytic lesions of the ventromedial hypothalamus were maintained at either 80% of their preoperative lean weights or 80% of their postoperative obese weights. Unlike sham-operated rats maintained at 80% of their weights, neither group of lesioned rats acquired schedule-induced polydipsia after 15 daily 1-h sessions on a free variable-interval 1-min food schedule with water continuously available. The results are consistent with previous findings of reduced drinking responses of ventromedially lesioned rats to a variety of conditions which increase drinking in normal rats.

Effects of ventromedial hypothalamic lesions on restricted feeding behavior in rats

Previous research has shown that VMH lesioned rats overeat when given free access to food yet undereat when daily access is restricted. In the present study VMH lesioned female rats in Experiment 1 and male rats in Experiment 2 consumed more food than controls during both free and restricted access feeding schedules. The factor that most likely accounts for the contrasting outcomes is the extent of hyperphagia displayed by the lesioned rats prior to restricted access feeding. The present data are consistent with the interpretation that VMH lesions increase hunger motivation.

Multiple effects of ventromedial hypothalamic lesions in the white-throated sparrow,Zonotrichia albicollis

Effects of ventromedial hypothalamic (VMH) lesions were studied in a migratory bird. A single lesion resulted in various combinations of physiological and behavioral responses, the most frequent being marked body weight gain, polydipsia and a failure to display gonadal development, prenuptial molt and Zugunruhe (nocturnal migratory restlessness). This variability in response implies that neural control mechanisms for each effect may be anatomically separable. Specific studies showed that water intake in one population was ten times control levels and was persistently greater for ten months. Locomotor activity was monitored before and after hypothalamic lesions. Ventromedial hypothalamic lesions selectively eliminated Zugunruhe. Termination of nocturnal activity was immediate, occurring the night following surgery.

Effects of ventromedial hypothalamic lesions on thyroid secretion rate in rats.

In male rats bilateral lesions of the ventromedial nucleus of the hypothalamus which cause significant increase in total body weight result in significant reduction in thyroid secretion rate. It is suggested that this reduction in thyroid secretion rate, along with growth hormone deficiency and hyperinsulinemia, may explain the increase in body fat which has been reported to occur in the hypothalamic obese rat.

Effects of ventromedial hypothalamic lesions on hunger-motivated behavior in rats.

Effects of ventromedial hypothalamic lesions on hunger-motivated behavior in rats.