Differential Circadian Eating Patterns in Two Psychogenetically Selected Strains of Rats Fed Low-, Medium-, and High-Fat Diets

Spontaneous eating patterns in male, inbred Roman high- and low-avoidance rats (RHA/Verh, RLA/Verh) were continuously recorded while animals were successively offered three isocaloric (16.5-kJ/g) diets: a low-fat, high-carbohydrate diet (LF; 3.3% fat), a medium-fat diet (MF; 18% fat), and a high-fat diet (HF; 40% fat), the latter being followed once again by the LF diet. Under the conditions of this experiment, overall 24h food intake did not differ significantly between RHA/Verh and RLA/Verh rats, but was significantly higher for both rat strains on the MF and HF diets than on the LF diet. Despite the similar 24h-food intake, RHA/Verh rats ate transiently less than RLA/Verh rats during the third quarter of the dark phase under all dietary conditions. These differences were due to the RHA/Verh rats' longer intermeal intervals (with all diets) and smaller meals (with the MF and HF diets) and were compensated for during the last 3 h of the dark phase. On the LF diet, dark-phase meal frequency was higher and both nocturnal meal size and mean eating rate within meals were lower in RLA/Verh rats than in RHA/Verh rats. With the MF and HF diets, mean nocturnal meal size and meal duration were higher and mean eating rate was lower in RLA/Verh rats than in RHA/Verh rats. For both strains, nocturnal meal size was significantly higher with the MF and HF diets than with the LF diet, and nocturnal meal frequency was lower with the HF diet than with the other two diets. Although body weights were similar at the start of the study, RLA/Verh rats gained significantly more weight than did RHA/Verh rats by the end. As has often been the case with other aspects of behavior studied, differences in neuromodulatory systems (e.g., serotoninergic and dopaminergic) between RHA/Verh and RLA/Verh rats may directly or indirectly contribute to the subtle differences in eating patterns observed here.     

Hepatic vagotomy disrupts somatotropin-induced protein selection

Rats treated with somatotropin (STH) and allowed to self-select between diets varying in protein content will consume more of the high-protein diet. The objective of this study was to determine the role of the hepatic vagus nerve in this ability to select protein. Female Sprague-Dawley rats (n=40) received a hepatic vagotomy (HVAGX) or a sham surgery. Postsurgery, the rats were maintained on pelleted diets for 2 weeks, after which the rats were adapted to selecting between powdered diets with 5% casein and 30% casein. After a 7-day adaptation to diet selection, rats in each surgical treatment group were treated with STH (4 mg/day) or physiological saline for 14 days. Body weight and intake were recorded daily. STH treatment increased growth rate to a similar degree in both sham and HVAGX groups. Despite causing an increase in total food intake, there was no effect of HVAGX alone on body weight. Relative to the sham-saline group, sham-STH in treated rats had greater total food intake that was accounted for entirely by increased consumption of the 30% protein diet and no change in intake of the 5% diet. In contrast, HVAGX+STH rats exhibited 20-30% increases in consumption of both the 5% and 30% protein diets. Thus, the HVAGX+STH rats recognized an increased need for protein, but were unable to distinguish between the high- and low-protein diets and selected more of both. The data suggest that the ability to alter diet selection in response to a stimulation of protein accretion is at least partially mediated through the liver and hepatic branch of the vagus nerve.     

The body weight loss of young rats caused by hepatic branch vagotomy is influenced by environmental temperature

Changes in body weight after hepatic branch vagotomy or sham vagotomy were examined in rats of three different body weights (about 100, 200 and 280 g), and it was noted that the weight loss was evident only in 100 g rats. In a second experiment, 100 g animals were hepatic branch vagotomized or sham operated and housed at three different room temperatures (12-17, 17-22, 22-27 degrees C). Subsequently, the reduction in weight of the vagotomized animal was correlated with the lowest room temperature in the vagotomized animal, and food intake was also decreased in direct relation to the temperature. The results suggest that there might be a hepatic vagal mechanism modulating food intake in young animals, and such a mechanism may be modulated by the environmental temperature.     

Changes in food intake after hepatic vagotomy at a stage of development in rats

Changes in food intake after hepatic vagotomy were examined in the body weights of three different rats (about 100, 200 and 280 g). The vagotomy reduced food intake only in the 100-g rats.     

Vagotomy produces learned food aversions in the rat

Subdiaphragmatic vagotomy produces hypophagia and weight loss in normal rats and can reverse the hyperphagia and obesity of rats with ventromedial hypothalamic lesions. Vagotomy surgery can also produce symptoms of nausea and discomfort. Since such symptoms are highly effective as unconditioned stimuli in food aversion conditioning, the present studies examined whether some of the depression in food intake observed in rats with vagotomy could be due to the development of aversions to the foods eaten after their surgery. In the first study, significant aversions developed to the specific novel diet consumed after vagotomy, results indicating that the symptoms associated with vagotomy can serve as effective unconditioned stimuli in the acquisition of learned food aversions. The second study compared vagotomized animals consuming familiar laboratory chow with those consuming a novel diet. In contrast to the novel diets, learned aversions did not develop to the familiar chow, and hypophagia was less persistent and severe. It is concluded that learned food aversions can contribute to the appetite and weight loss exhibited by vagotomized animals. Consideration of the conditions under which these aversions arise after vagotomy surgery may allow for the design of studies so as to minimize the aversions and thereby separate these nonspecific effects from direct regulatory deficits produced by vagotomy.     

Influence of vagotomy in domestic fowls on feeding activity, food passage, digestibility and satiety effects of two peptides

The effects of bilateral vagotomy at the level of the proventriculus, in immature female fowls (VAG), on body weight, feeding activity parameters, rate of food passage, digestibility, and satiety effects of bombesin (BBS) and cholecystokinin octapeptide (CCK8), were compared with those in sham-operated controls (SHAM). SHAM birds gained weight at a greater rate postoperatively than before their operation, whereas VAG birds did not. Daily food intake did not change significantly as a result of the operation with either SHAM or VAG birds, and the only effect on feeding activity parameters was on the length of intermeal intervals, which increased in VAG birds. Rate of passage of the layers' mash diet was slower, and its apparent digestibility lower, in VAG than in SHAM birds. Short-term suppression of food intake, following intravenous injections of BBS (10 micrograms/kg) or CCK8 (10 micrograms/kg), did not differ between SHAM and VAG birds. The different postoperative weight gains may have been a consequence of different weights of food digested, and the difference in interval length was probably due to the different rates of food passage. The results of these experiments indicate that efferent information affecting rate of passage and digestibility travels via the vagus, but that afferent information concerned with initiation and termination of meals, and with satiety effects of BBS and CCK8, does not. Instead, such afferent information may travel via the intestinal nerve, which is unique to birds.     

Afferent signalling through the common hepatic branch of the vagus inhibits voluntary lard intake and modifies plasma metabolite levels in rats

The common hepatic branch of the vagus nerve is a two-way highway of communication between the brain and the liver, duodenum, stomach and pancreas that regulates many aspects of food intake and metabolism. In this study, we utilized the afferent-specific neurotoxin capsaicin to examine if common hepatic vagal sensory afferents regulate lard intake. Rats implanted with a corticosterone pellet were made diabetic using streptozotocin (STZ) and a subset received steady-state exogenous insulin replacement into the superior mesenteric vein. These were compared with non-diabetic counterparts. Each group was then subdivided into those whose common hepatic branch of the vagus was treated with vehicle or capsaicin. Five days after surgery, the rats were offered the choice of chow and lard to consume for a further 5 days. The STZ-diabetic rats ate significantly less lard than the non-diabetic rats. Capsaicin treatment restored lard intake to that of the insulin-replaced, STZ-diabetic rats, but modified neither chow nor total caloric intake. This increased lard intake led to selective fat deposition into the mesenteric white adipose tissue depot, as opposed to an increase in all visceral fat pad depots evident after insulin replacement-induced lard intake. Capsaicin treatment also increased the levels of circulating glucose and triglycerides and negated the actions of insulin on these and free fatty acids and ketone bodies. Collectively, these data suggest that afferent signalling through the common hepatic branch of the vagus inhibits lard, but not chow, intake, directs fat deposition and regulates plasma metabolite levels.     

Influence of anterior subdiaphragmatic vagotomy and TPN on rat feeding behavior.

Total parenteral nutrition (TPN) inhibits food intake and feeding behavior. Whether caloric sensory function of the liver contributes to this food intake and feeding behavior regulation via vagal-afferent innervation was tested after performing anterior hepatic vagotomy or sham operation in rats infused with a TPN solution providing 100% of daily energy needs, given continuously for 4 days. Food intake, meal number, size, duration, meal and intermeal sniffs, and eating activity were measured using an automated computerized rat eater meter (ACREM). TPN infusion resulted in a significant decrease of food intake and feeding indexes in both groups. The vagotomized rats showed a significantly higher food consumption, achieved by greater meal frequency, larger meal size, and longer meal duration. Thus, vagotomized rats consumed more than their controls by eating larger meals more often and of longer duration. Data suggest that anterior hepatic vagotomy interrupts hepatic caloric sensory feedback loop, diminishing inhibitory vagal effects on food intake with TPN, leading to an overall increase in food intake.     

Lesion of vagal afferent terminals impairs glucagon-induced suppression of food intake

Selective hepatic branch vagotomy impairs glucagon-induced inhibition of food intake. However, the relative importance of afferent and efferent neurons in glucagon satiety has not been directly investigated. In this experiment, lesions were placed in the area postrema (AP) and immediately subjacent nucleus of the solitary tract (NTS) where hepatic vagal afferents have been reported to terminate. We found that these lesions impaired glucagon-induced satiety under testing conditions similar to those that reveal a glucagon satiety deficit in rats with selective hepatic branch vagotomies. Since these lesions did not damage the underlying dorsal motor nucleus of the vagus, our results suggest that our AP/NTS lesions impaired glucagon satiety by damaging terminal fields of vagal afferent neurons. Finally, our lesions did not impair satiety induced by cholecystokinin (CCK), a response mediated by gastric vagal afferent neurons. This latter result suggests that the vagal afferent terminal fields required for glucagon- and CCK-induced satiety are not coextensive.     

Truncal and hepatic vagotomy reduce suppression of feeding by jejunal lipid infusions

Two experiments investigated mechanisms underlying the decrease in food intake produced by lipid infusions into the jejunum. In Experiment 1, male Sprague-Dawley rats with truncal abdominal vagotomy (TVx), selective hepatic-branch vagotomy (HVx), or sham vagotomy received repeated 7 h infusions of linoleic acid (LA), corn oil (CO), or saline through indwelling jejunal catheters. Cumulative food intake was measured at 1, 3, 6, and 23 h. LA and, to a lesser extent, CO suppressed food intake in excess of the caloric value of the load. This effect was eliminated by TVx, which significantly attenuated the suppression of intake produced by both lipids at 3 and 6 h and also at 23 h when LA was infused. HVx attenuated suppression at 23 h on tests with LA and at 3 and 6 h on CO tests. Experiment 2 showed that jejunal infusion of LA had no effect on multi-unit activity of afferent fibers in the left splanchnic nerve in anesthetized rats. Thus, these results provide further evidence that satiating effects of intestinal lipid infusions are mediated by the vagal fibers, some of which lie within the hepatic branch. However, because significant suppression of food intake remained after TVx, and because of the negative results of Experiment 2, these lipid infusions engage as yet unidentified mechanisms independent of the vagus.     

Aversive effects of vagotomy in the rat: a conditioned taste aversion analysis

Subdiaphragmatic vagotomy suppresses food intake and water intake in normal rats. Since human patients report some nausea and discomfort following vagotomy, the present study assessed the aversive consequences of vagotomy in rats using a conditioned taste aversion paradigm. Rats were given a total subdiaphragmatic vagotomy or sham vagotomy, and were then maintained on either plain water (Vag-Water and Sham-Water groups) or a novel cherry solution (Vag-Cherry and Sham-Cherry groups). When subsequently tested for their water vs. cherry preferences on postoperative days 6, 16, and 26, the Vag-Cherry group displayed a greater aversion to the cherry solution than did the remaining three groups. This result suggests that vagotomy produces visceral malaise in rats which may contribute to the feeding and drinking suppressive effects of the surgery.     

CCK inhibits real and sham feeding in gastric vagotomized rats

We tested both sham feeding and real feeding in gastric vagotomized rats equipped with chronic gastric cannulas, either without pretest food deprivation or after 18 hr food deprivation. In each condition, 0.3-4 micrograms/kg CCK inhibited food intake similarly in control and vagotomized rats. Behavioral observations indicated the presence of normal postprandial satiety after CCK. We then tested real feeding in noncannulated rats after either total abdominal vagotomy, gastric vagotomy, or control operation. Doses of 0.5-4 micrograms/kg CCK had no effect on food intake after total vagotomy, but again inhibited feeding with equal potency in gastric vagotomized and control rats. The inhibitory effect of 6 micrograms/kg CCK was attenuated but not blocked by total vagotomy. Finally, we tested rats with gastric cannulas after gastric plus celiac vagotomy. CCK also inhibited both real and sham feeding after this lesion. These data confirm previous findings that abdominal vagal fibers mediate the satiety effect of moderate intraperitoneal doses of CCK, but fail to support the hypothesis that gastric branch fibers are the necessary vagal contribution.     

Subdiaphragmatic vagal deafferentation fails to block the anorectic effect of hydroxycitrate

We investigated the neural mediation of the feeding suppression through orally administered hydroxycitrate (HCA) in male rats that were fed a high-glucose diet (about 48% glucose). Ten-day ad libitum food intake and body weight regain after previous body weight loss (13% of initial body weight) due to restrictive feeding were measured in rats with sham deafferentation (SHAM; n = 6), subdiaphragmatic vagal deafferentation (SDA; n = 7), and SDA plus celiac-superior mesenteric ganglionectomy (SDA/CGX; n = 9). HCA suppressed the 10-day cumulative food intake in all surgical groups and body weight regain in SDA and SDA/CGX groups. Independent of HCA, SDA and SDA/CGX rats consumed less food and gained less weight compared to SHAM rats. These results demonstrate that all vagal afferents from below the diaphragm and vagal efferents of the dorsal trunk as well as splanchnic nerves (afferents and efferents) are not necessary for the feeding-suppressive effect of HCA in this animal model. Vagal afferents, however, appear to play a role in the control of intake when a high-glucose diet is consumed after a period of restrictive feeding.     

Hepatic branch vagotomy attenuates the feeding response to 2-deoxy-D-glucose in rats

The effect of hepatic branch vagotomy on the feeding response induced in rats by intraperitoneally injected 2-deoxy-D-glucose (2-DG) was tested. Injections were given 1 h after onset of the dark phase, and immediately [corrected] after the rats had ingested a meal. 2-DG produced a smaller feeding response in hepatic branch-vagotomized rats compared with that in sham-vagotomized rats. This finding suggests that hepatic glucoreceptors with vagal afferent fibres are involved in the feeding response to glucose deprivation.     

Effect of type of protein on food intake of rats fed high protein diets

The effects of type of protein on intake of a high protein diet after adapting rats to a low protein diet were examined in rats trained to eat a 5.2% (N X 6.25) protein diet containing a mixture of casein, lactalbumin, egg white and soy protein, in a single 3-hour period per day. Food intake was measured from 0-15, 15-30, 30-90, and 90-180 minutes. After a 2-week adjustment period, rats were presented with a 40% (N X 6.25) protein purified diet containing only one of the 4 proteins mentioned above or a mixture of these 4 proteins. During the first 15-minute interval, rats eating diets containing protein mixture, lactalbumin, egg white or soy protein depressed their intake significantly compared with the average intake of the 3-day pre-test period, whereas rats eating casein diet increased their intake. During the last 90-minute interval of the first day, all rats depressed their intake, those rats eating casein the least and those rats eating egg white the most. On the second day, rats offered lactalbumin depressed their intake 52.5% for the 3-hour period and rats offered casein depressed their intake 34.3%. Rats eating soy protein, egg white and protein mixture increased their intake from day 1 to day 2. These experiments show that type of protein affects rats' initial intake when they are offered a high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serotonin-depleting midbrain lesions do not prevent ovariectomy-induced weight gain.

Past research has shown that subdiaphragmatic vagotomy and midbrain raphe lesions are each effective in impeding the development of hypothalamic obesity while neither affects the development of genetic obesity in Zucker rats. To further test the parallels that may exist between these two manipulations on another putative obesity model, we studied the effects of midbrain raphe lesions on the development of ovariectomy-induced weight gain, previously shown to be unaffected by vagotomy. Ten adult female rats received thermal lesions of the dorsal and median raphe nuclei (RAPHE) while 7 served as sham controls (SHAM). Following a 26-day recovery period during which body weight, food intake and water intake were periodically monitored, bilateral ovariectomy (OVX) was performed on 7 RAPHEs and 4 SHAMs, with laparotomy (LAP) being performed on 3 RAPHEs and 3 SHAMs. Body weights and intake variables were monitored for an additional 58 days, then animals were sacrificed for brain histological and biochemical assessments. RAPHEs weighed less despite eating and drinking more than SHAMs throughout this study. Nevertheless, OVX rats gained more weight regardless of lesion (mean +/- SEM weight gain = 73.9 +/- 5.5 g for RAPHE + OVX and 67.0 +/- 6.6 g for SHAM + OVX vs. 30.7 +/- 3.0 g for RAPHE + LAP and 39.7 +/- 5.5 g for SHAM + LAP). This occurred without reliable changes in the food or water intakes of either OVX subgroup. Histology confirmed that RAPHE lesions were largely localized to the dorsal and median raphe nuclei, as planned.(ABSTRACT TRUNCATED AT 250 WORDS)     

Feeding and macronutrient selection patterns in rats: adrenalectomy and chronic corticosterone replacement

To analyze further the role of corticosterone (CORT) in the control of feeding behavior, we examined the impact of adrenalectomy (ADX) and chronic CORT implants on the food intake and macronutrient self-selection patterns of adult male rats at different periods of the diurnal cycle. Consistent with a separate study of acute CORT injection in ADX rats (Kumar and Leibowitz, 1988), the present findings indicate that ADX significantly attenuated the rats' daily (24 hr) ingestion of all three macronutrients, namely, protein, carbohydrate and fat. However, food intake in the dark cycle, specifically during the first few hours after dark onset, was significantly more affected (-70%) than feeding in the later dark and light periods (-25%). Moreover, during this early dark time when circulating CORT level normally peaks, ADX appeared to have its strongest suppressive effect on carbohydrate ingestion. Chronic subcutaneous CORT implants in the ADX animals reversed these effects of surgery and generally restored the rats' eating patterns to that of the cholesterol-implanted SHAM animals. These findings suggest that CORT exerts a decisive influence on caloric intake, on the diurnal pattern of feeding, and on appetite for specific macronutrients. The impact of CORT on carbohydrate intake is apparent specifically during the active eating period, particularly at dark onset when endogenous CORT levels normally peak and carbohydrate is exhibited as the preferred macronutrient.     

Changes in salt intake after abdominal vagotomy: Evidence for hepatic sodium receptors

Several reports have suggested that the mammalian liver contains neural receptors, innervated by the vagus nerve, that monitor the sodium concentration and osmolarity of the portal circulation. These reports have been concerned primarily with either the neurophysiological identification of these receptors or their role in the short term control of urine output. Inasmuch as relatively little is known about the role of these receptors to consummatory behavior, we investigated the effects of hepatic vagotomy in rats on sodium intake as well as on sodium output. Hepatic vagotomized (HV) rats drank less NaCl solution (0.03, 0.1, 0.3M) in 24 hr during a two-bottle test with water than sham operated rats. Comparable differences in the intakes of either water, KCl or glucose solutions were not found. The two groups of rats did not differ in their intakes of water or 0.3M NaCl after an injection of either an osmotic load (IP, 2 M NaCl, 1% BW), deoxycorticosterone acetate (SC, 5 mg) along with furosemide (SC, 10 mg), or after 10 days of sodium deprivation. Urinary sodium output was reduced in HV rats during sodium deprivation but not when the rats had adequate levels of sodium in their diet. Because circadian patterns of water and food intake as well as body weight growth of hepatic vagotomized rats were similar to those of control rats, general malaise due to surgery and generalized deficits in motivation were ruled out as explanations for the depressed daily drinking of NaCl solutions. These findings support the existence of hepatic sodium receptors and their possible involvement to the control of sodium regulation.     

Hepatic gluconeogenesis in rats trained to eat a single meal daily. Role of eating periodicity and the amount of food ingested in the last meal

Rats trained to eat a single daily meal (MF rats), from 8:00-10:00 a.m., increased food intake from the 1st to the 12th (125%) day of feeding training. In this work we compared the influence of the higher food ingestion in the last meal and feeding training on hepatic gluconeogenesis. Thus, rats at the 1st (MF(1st day-5g) group) and 13th day (MF(13th day-5g) group) of training, refed with a fixed amount of food (5g) were employed. In addition, a third group of MF rats, refed on day 12 with 75% (12g) of the food ingested by MF rats on the 13th day of the feeding training (MF(13th day-12g)) was included. The experiments were performed at 22 h after meal (8:00 a.m.). Our results demonstrated that feeding training had a crucial role in determining gluconeogenesis from pyruvate (5 mM). Additionally, gluconeogenesis from L-glutamine (5 mM) was influenced by periodicity of eating and the amount of food ingested in the last meal. In contrast, gluconeogenesis from L-alanine (5 mM) was not influenced by both factors. In conclusion, our findings suggested that the hepatic gluconeogenesis was influenced by food ingestion and/or feeding training depending of the substrate investigated. These effects on gluconeogenesis may have implications for use in diabetic regimens.     

Effects of selective vagotomies on knife cut-induced hypothalamic obesity: Differential results on lab chow vs high-fat diets

Asymmetrical hypothalamic knife cuts were used to produce obesity in rats fed lab chow pellets. When the brain surgery was accompanied by selective section of the coeliac branch of the abomdinal vagus nerve, only 57% of the expected weight gain was observed. Additional section of the gastric branches of the vagus further reduced the knife cut effects, and complete subdiaphragmatic vagotomy suppressed body weight below control levels. Conversely, all vagotomies that spared the coeliac branch did not by themselves attenuate hypothalamic knife cut obesity. These results suggest that some function(s) under coeliac vagal control are specifically involved in mediating hypothalamic hyperphagia and obesity. When, after 30 days, the rats were switched to high-fat diet, all the knife cut rats overate and became obese (or more obese) irrespective of vagotomy status. This overeating despite vagotomy indicates that the vagus nerves must not be the exclusive mediator of hypothalamic obesity.