Diet selection following area postrema/nucleus of the solitary tract lesions

Ten adult Long-Evans male rats were offered access to fat, protein and carbohydrate from separate sources. After adaptation to this diet, 5 animals received thermal lesions of the area postrema and adjacent caudal-medial portion of the nucleus of the solitary tract (AP/cmNTS). The remainder were sham-operated. AP/cmNTS lesioned rats ate significantly less and lost more weight than controls during the first postsurgery measurement period (Days 4–13 after lesioning). The decrease of food intake of AP/cmNTS lesioned rats was due to reduced fat consumption. Carbohydrate and protein intakes of lesioned animals did not differ from those of controls. Food intakes and weight changes of lesioned rats did not differ from those of controls during days 14–23 after lesioning. Intake of fat by lesioned animals remained low but was no longer significantly different from that of controls. Carbohydrate and protein intakes of lesioned rats increased slightly but did not differ significantly from those of nonlesioned controls.     

Effects of hippocampal lesions on adaptive intake of diets with disproportionate amounts of amino acids

Bilateral double electrolytic overlapping lesions were placed in dorsal-lateral hippocampus of male 230 g rats, and their food intake responses to the ingestion of diets containing disproportionate amounts of amino acids were examined. Rats with such lesions and intact control rats maintained their normal intakes of the 6% casein basal diet or a threonine basal amino acid diet postoperatively. However, they exhibited marked initial food intake depression, similar to that of intact rats, when fed the threonine imbalanced amino acid diet. Also, animals with lesions in certain areas of the dorsal-lateral hippocampus showed facilitated adaptation to the amino acid imbalanced diet. Similar severe reduction in food intake with relative lack of adaptation were observed in both the intact controls and rats with hippocampal lesions when fed amino acid diets completely devoid of threonine. Initial food intake of rats with hippocampal lesions was inhibited drastically as was the case with the intact controls when fed a 75% casein high protein diet. All rats, either intact or lesioned, showed similar slow adaptation patterns with the prolonged ingestion of the high protein diet. The initial food intake responses and facilitated adaptation of the animals bearing lesions in certain areas of the hippocampus suggest that such areas are not crucially involved in the inhibition of food intake of rats fed disproportionate amounts of dietary amino acids. Rather, such areas of lesions in the hippocampus may play a role in a system governing the behavioral adaptation of the intake of amino acid imbalanced diets but not of diets containing amino acids in general excess. This would also indicate that different mechanisms control the intake of amino acid imbalanced diets and diets containing amino acids in excess.     

Regulation of calorie intake in rats with rostral zona incerta lesions: effects of caloric density or palatability of the diet

Following an initial period of hypophagia, the body weights of rats with zona incerta lesions approached asymptotic levels that were significantly lower than those of controls although daily food intake was not reliably depressed. In spite of persisting deficits in feeding efficiency, the ad libitum food intake of the ZI-lesioned rats (relative to body weight) recovered to preoperative levels and was regulated accurately with respect to the caloric density of the diet. However, rats with ZI lesions were finicky eaters and did not maintain stable calorie intake when given unpalatable diets. The water intake of ZI-lesioned rats remained consistently below that of neurologically intact rats but was normal relative to their own food intake and lowered body weight.     

Cingulate lesions and behavioral adaptation to amino acid imbalanced diets

The effect of anterior cingulate cortex lesions on dietary intake and adaptation of disproportionate amounts of amino acids was examined. Rats with bilateral electrolytic lesions in the anterior cingulate cortex and sham-operated rats were fed, in turn, amino acid basal, imbalanced or devoid diets involving threonine and isoleucine as the growth limiting amino acids, and then a low protein (6% casein) followed by a high protein (75% casein) diet. Lesions of the anterior cingulate cortex did not prevent the initial depression in food intake of the amino acid imbalanced diets, but shortened the duration of anorexia associated with dietary amino acid imbalances. Cingulate lesions did not influence the food intake of rats fed amino acid devoid diets. When switched from a low protein to a high protein diet, animals bearing lesions and sham-operated controls reduced markedly their initial food intake and adapted to the high protein diet in similar manner. It was concluded that the initial food intake depression associated with a dietary amino acid imbalance is a direct response to postingestive cues which influence food intake. Moreover, that the difference in adaptive intakes of the cingulate cortex lesioned animals who ingested a diet of imbalanced amino acids or of high protein, indicates that separate mechanisms act to control food intake of animals fed diets containing imbalanced amino acid mixtures or diets with excessive amounts of protein.     

Effects of area postrema/caudal medial nucleus of solitary tract lesions on food intake and body weight

Lesions of the area postrema/caudal medial nucleus of the solitary tract (AP/cmNTS), located on the surface of the dorsal medulla of the rat, cause a transient syndrome of hypophagia and body weight loss, with the establishment of a new growth curve at a lower body weight set point. The regulatory responses to prolonged food deprivation, glucoprivic stimulation, and chronic access to a palatable diet are left largely intact. However, there is an overconsumption of highly palatable foods during acute exposure to supermarket and high-fat diets. Intestinal transit and gastric retention are unaffected by the lesion, indicating normal motor function within the gastrointestinal system. The hypophagia and chronic depression of body weight by the AP/cmNTS lesion demonstrate that this area is an important part of the larger neurocircuitry subserving feeding behavior and energy balance.     

Caloric compensation in hypothalamic obese rats

The present study explored the influence of pelleted diets on adjustment to caloric dilution in hypothalamic obese rats. Medial hypothalamic lesioned and normal rats were maintained on a high fat diet until the static stage of hyperphagia was reached. They were given three pelleted diets which consisted of undiluted Noyes pellets and Noyes pellets diluted 25 or 50 percent with kaolin. In contrast to previous reports that hypothalamic obese rats do not compensate for caloric dilution of their diet, the obese animals showed as large an increase in food intake on the dilute pelleted diets as did the control animals. These results were interpreted by viewing texture as a dimension of palatability which influences food intake in hypothalamic obese rats.     

Effect of amygdaloid lesions on dietary intake of disproportionate amounts of amino acids

Male rats with bilateral electrolytic lesions in the anterior, medial or posterior aspects of the ventral amygdala and groups of intact rats were fed, in turn, basal, imbalanced or deficient amino acid diets involving threonine or isoleucine as the limiting amino acid, and then a low protein (6% casein) followed by a high protein (75% casein) diet. No change in food intake was observed in animals fed the threonine basal diet postoperatively. When the threonine or isoleucine imbalanced diet was substituted for the respective basal diet, animals with lesions in certain areas of the medial amygdala showed little or no depression in food intake of the imbalanced diets, while all other rats with amygdala lesions reduced their food intake markedly, as did intact controls, when fed such diets. All animals, however, curtailed their food intake of the deficient or high protein diets. The lack of responsiveness of the animals with medial amygdaloid lesions to the imbalanced diets suggests that these areas may be involved in a system regulating food intake of animals fed diets containing imbalanced amino acid mixtures.     

Area postrema lesions produce feeding deficits in the rat: Effects of preoperative dieting and 2-deoxy-D-glucose

To investigate the possible role of the area postrema (AP) in the control of food intake and body weight, male albino rats were divided into four groups: (a) animals dieted to 80% of their original body weights prior to receiving AP lesions, (b) nondieted animals with AP lesions, (c) animals dieted to 80% prior to receiving sham lesions, and (d) nondieted animals with sham lesions. Lesions of the AP in nondieted rats resulted in hypophagia, hypodipsia and body weight loss followed by recovery of normal intake and maintenance of body weight at a fixed percentage of the sham operated animals' weight. Reducing body weight prior to surgery led to body weight maintenance levels equivalent to those of the nondieted groups. We also tested the animals for sensitivity to glucoprivation caused by intraperitoneal injections of 2-deoxy-D-glucose (2-DG). Injections of 2-DG produced hyperphagia in sham lesioned rats, but not in rats with AP lesions. Our data suggest that the effects of AP lesions on intake and body weight are similar, in several important respects, to the lateral hypothalamic feeding syndrome and to the effects of subdiaphragmatic vagotomy. We discuss the results with respect to hierarchical levels of neural circuitry involved in controlling feeding behavior.     

The orexigenic effect of peripheral ghrelin differs between rats of different age and with different baseline food intake, and it may in part be mediated by the area postrema

Ghrelin is mainly secreted during fasting. While an orexigenic effect of peripherally injected ghrelin has been reported, reproducing this effect has often proven difficult. Here, we hypothesized that ghrelin's effect to increase food intake may depend on the experimental conditions (e.g., age of animals). We therefore investigated the effect of an IP ghrelin injection (100 microg/kg) on food intake in rats of different age and at different times during the light-dark cycle, i.e. with different levels of baseline food intake. Ghrelin injected at dark onset in ad libitum fed young rats (body weight [BW] 92 g) slightly increased feeding while no such effect was observed in 12 h food deprived rats (BW 150 g). In the middle of the light phase, ghrelin significantly increased feeding up to 2 h after injection in ad libitum fed rats (BW 130 g; food intake 1 h after injection: NaCl 0.4 +/- 0.2 g versus ghrelin 1.2 +/- 0.3 g [p < 0.05]). In various subsequent experiments, older rats (BW 300-490 g) tested under the same conditions did not respond to a single ghrelin injection. However repeated ghrelin injection (15 microg/kg/day once daily at light onset) over 10 days significantly increased food intake in rats (BW 400-460 g) starting from day 4 of the experiment (24 h food intake: NaCl approx. 19.5 g, ghrelin 22.5 g). Interestingly, the latter effect was completely abolished in rats lesioned in the area postrema (AP). Cumulative food intake was also increased in SHAM but not in AP-X animals (e.g., after 7 days: SHAM/NaCl 135.1 +/- 5.3 g versus SHAM/ghrelin 149.7 +/- 3.5 g [p < 0.05], AP-X/NaCl 127.2 +/- 16.4 versus AP-X/ghrelin 127.9 +/- 5.3). We conclude that ghrelin's effect to increase food intake can best be demonstrated when basal food intake is low. Ghrelin increases feeding mainly in young, fast growing animals. Ghrelin may therefore link the high energy needs to body growth in young individuals. In older animals, peripheral ghrelin increased feeding when injected repeatedly over several days. At least under these conditions, ghrelin's effect was mediated by the AP/NTS region. Using repeated administration, ghrelin might be an interesting tool to increase feeding in patients suffering from wasting diseases such as cancer anorexia.     

Enhanced saline intake and decreased heart rate after area postrema ablations in rat

The area postrema (AP) is a circumventricular organ located in the dorsal medulla. Previous studies found that AP lesions lead to increased saline ingestion in the rat. The salt appetite was thought to be a result of primary disruptions in sodium regulation or in cardiovascular regulation. To assess this we measured food and fluid intakes, urinary electrolyte and aldosterone concentration, and blood pressure and heart rates in AP lesioned and control animals during a period of normal sodium intake and during a period of excessive sodium intake. Rats with AP lesions exhibited sodium appetite but not natriuresis. In fact, sodium intake greatly exceeded output. Their urinary aldosterone levels were similar to those of control animals during both periods. The lesioned rats also had lowered heart rates, yet, their blood pressures were similar to control animals. These results are discussed with reference to a possible role of the AP in satiety and in maintaining homeostasis.     

Preabsorptive factors are not the main determinants of intake depression induced by a high-protein diet in the rat

The factors involved in the depression of food intake produced by a high-protein diet are still poorly understood. The aim of this study was to assess the role of several preingestive or preabsorptive factors likely to influence food intake when rats were fed ad libitum. Food intake was measured after modifying the composition of the high-protein diet, i.e., the type of proteins, or carbohydrates. Moreover, correlations between high-protein diet intake and the quantity of fluid ingested or stomach volume were studied. By varying the carbohydrate composition (sucrose/cornstarch) and the protein source (soy or gluten or total milk protein) of high-protein diets, we modified the orosensory properties of these diets. However, no differences in food intake were observed between these groups of rats during the transition phase or after adaptation, except during the first day of soy- or gluten-based diets when the depression of food intake was intensified. The depression of high-protein diet intake was neither the consequence of any delay necessary to increase the fluid intake induced by eating a high-protein diet nor due to a marked increase in stomach volume, which might explain enhanced satiety and decreased food intake through the activation of vagal afferent fibers. Our experiments do not indicate a preponderant role for oropharyngeal or preabsorptive factors in the depression of food intake induced by a high-protein diet.     

Lack of diet-induced thermogenesis in brown adipose tissue of obese medial hypothalamic-lesioned rats

Radiofrequency heat lesions were made in the medial hypothalamus of 12-week old male and female Holtzman rats. Two to three days later rats were offered a palatable cafeteria diet in addition to chow or were fed chow alone for the next 3-4 weeks. Male lesioned rats were only slightly hyperphagic on the chow diet and gained little extra weight. When fed the cafeteria diet, energy intake of male lesioned rats almost doubled in comparison with chow-fed lesioned rats and a very rapid extra weight gain occurred. Despite the marked hyperphagia, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed lesioned rats, as indicated by low mitochondrial guanosine diphosphate (GDP) binding. In female rats, lesions induced much greater hyperphagia and body weight gain than in male rats, particularly when they ate the cafeteria diet. Again, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed female lesioned rats. The proportion of energy derived from carbohydrate was not altered by the cafeteria diet in either male or female rats, whether lesioned or not, but there was an increase in the proportion of energy derived from fat at the expense of protein. No sex differences in food selection were observed. The accumulation of body fat was always greater in female lesioned rats than in male lesioned rats for similar food intakes. It is concluded that medial hypothalamic lesions prevent the normal occurrence of diet-induced thermogenesis in brown adipose tissue despite extreme overeating by the rats of a palatable cafeteria diet.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

Effect of guanethidine sympathectomy on intake and body weight of intact and LHA-lesioned rats

The present study investigated the role of direct sympathetic nervous system innervation of the viscera in the reduced body weight levels maintained by animals bearing lesions of the lateral hypothalamic area (LHA). Adult, male rats with, and without, electrolytic lesions of the (LHA) were treated with guanethidine sulphate (25 mg/kg IP daily for 6 weeks) to produce destruction of the peripheral sympathetic nervous system. LHA-lesioned rats displayed the expected reduced body weight compared to intact rats. Sympathectomy in lesioned rats resulted in an identical pattern of effects to that seen in intact rats. Transitory reductions in intake were effected and weight was significantly depressed by one week of guanethidine treatment. However, weight had recovered to control levels in both intact and lesioned drug-treated groups by the end of the experiment. The reduced body weight level maintained by LHA-lesioned rats was not altered by guanethidine sympathectomy. The major conclusions are (1) the reduced body weights maintained following LHA lesions are not dependent upon an intact sympathetic nervous innervation of visceral organs, and (2) peripheral sympathectomy in intact adult rats has no chronic effects on either body weight or food and water intake.     

Sham feeding is inhibited by dietary-induced obesity in rats

A group of six female, albino rats were maintained on a cafeteria diet of cookies, milk, and elevated-fat (shortening), rat-chow mixture and rat chow while a similar group received only rat chow ad lib for 17 weeks. When the groups differed significantly in mean body weight (obese-387.5 g, controls-287.2 g; p less than 0.001), gastric fistulas were implanted in each animal. After recovery, the rats were adapted to a liquid diet and assessed for sham feeding. Control-fed, normal-body-weight subjects showed substantial sham feeding when ingesting the Vivonex with the fistulas open compared to fistula-closed intake; meal frequency, meal size (apart from the initial meal) and total food intake were significantly increased while the satiety ratios following each meal were significantly decreased. Obese animals showed no significant increased feeding and satiety ratios were unreliably altered; while normal-body-weight controls increased 4-hr food intakes by 93% and halved their mean satiety ratios the obese animals showed an 8% increase in 4-hr food intake and only a 22% decrease in mean satiety ratios. We offer the hypothesis that, when animals are induced to become obese by palatable and varied diets which are then terminated, the anorexia produced is independent of gastrointestinal interactions inasmuch as that anorexia extends to sham feeding.     

Nocturnal feeding pattern in the prepubertal rat: influence of the ventromedial hypothalamus (VMH)

Daily feeding patterns, food intake and changes in body weight of male and female prepubertal rats were observed across a period from 21 to 50 days of age. Light/dark differences in feeding were found for both males and females throughout the recorded period, with feeding occurring predominantly during the dark period. The light/dark difference in feeding behavior gradually increased as the animals developed. Bilateral lesions placed in the VMH of female rats at 21 days of age disrupted the light/dark differences in feeding behavior primarily by decreasing dark period feeding. These lesions further resulted in a period of hypophagia and retarded body weight gain as well as a delay in pubertal onset. These data indicate that prepubertal rats regulate their feeding behavior so that food intake occurs principally during the dark period and that the integrity of the VMH is necessary for this regulation.     

Effects of diet and exercise training on thermogenesis in adult female rats

The effects of a cafeteria diet on body weight gain, food intake, resting metabolic rate (RMR) and the thermic effect of food (TEF) were compared in female Charles River albino rats that were either sedentary or exercise-trained. The food intakes of the exercise-trained rats on the cafeteria diet were increased to the same degree as those of the sedentary rats, however, they gained less body weight and body fat than sedentary controls. The exercise training increased RMR independent of diet, but differentially increased TEF in rats given the cafeteria diet. Conversely, sedentary rats on the cafeteria diet had significantly lower RMR, but their TEF were not different from control animals on lab chow. Thus, in addition to the direct cost of the exercise, training increased thermogenesis (RMR and TEF) which also helped prevent the dietary obesity which normally occurs with cafeteria diets.     

Pancreatic glucagon and postprandial satiety in the rat

The hypothesis that administration of pancreatic glucagon inhibits feeding by eliciting satiety for food was tested against several behavioral and physiological criteria of specificity. The effects of intraperitoneal glucagon injections on intake of a palatable milk diet were tested in rats maintained with ad lib access to pelleted diet. Injections of 25–800 μg/kg glucagon administered at meal onset inhibited meal size by 17–36%, but did not affect the normal postprandial behavioral satiety sequence or elicit any behavioral signs of toxicity. Latency to rest and intermeal interval were not affected. Glucagon decreased meal size by specifically inhibiting feeding during the terminal phase of the meal without affecting feeding earlier in the meal. This was also the case when glucagon was injected 4 min prior to meal onset. This range of glucagon doses did not affect water intake in water deprived rats consuming fluid volumes comparable to the milk intakes. They also did not affect body temperature. Finally, injection of 400 μg/kg glucagon after the initial exposure to a novel drinking fluid was not sufficient to form a conditioned taste aversion in a two bottle preference test. These data, together with reports that circulating pancreatic glucagon levels increase during meals, strongly suggest that pancreatic glucagon is involved in the production of postprandial satiety.     

Effect of insulin in rats with lesions of the dorsomedial hypothalamic nucleus.

Four hours after insulin injection Dorsomedial Hypothalamic Nuclei (DMN) lesioned rats consumed an amount of food that was comparable to that eaten by injected sham-operated animals. However, the DMN lesioned rats are not as initially responsive to the food intake stimulating properties of insulin as are the controls. A second study showed ad lib fed and fasted lesioned animals displayed a lower plasma glucose concentration after insulin challenge than did respectively treated controls. This suggests the initial insulin-induced feeding of the lesioned rats was blunted when compared to the controls even in the face of lower plasma glucose levels. Although a previous investigation revealed that DMN lesions destroy glucoreceptor tissue, the present data shows that DMN lesioned rats will increase their food intake in the face of insulin challenge, albeit their initial feeding response to insulin challenge is somewhat blunted. Finally, the present study confirms a previous report in that DMN lesioned rats can competently meter their 24 hour calorie intake.     

Palatability and caloric density as determinants of food intake in hyperphagic and normal rats

Female albino rats with lesions of the ventromedial hypothalamus and without any lesions were presented with powdered diets, the caloric density and palatability of which were varied independently by adding kaolin and sodium saccharin or confectioner's sugar. As the dilution of the unsweetened diet increased above 20% the lesioned rats decreased food consumption more than did the controls, and they increased consumption less than did the controls over successive days of exposure to the diluted diets. Sweetening the dilute diets usually produced a larger increase in food consumption among the hyperphagic rats, especially those in the dynamic phase, than among their controls. The data are interpreted in terms of the hypothesis that lesions of the ventromedial hypothalamus remove or attenuate the long term influence of nutritional balance, leaving body weight to be adjusted to a set point defined by the interaction of prevailing values of other stimuli such as diet palatability that are known to influence initiation and termination of eating.