V.E. Mendel

Effect of Meal Feeding on Daily Rhythms of Plasma Corticosterone and Growth Hormone in the Rat

After rats had adapted to regular meal feeding in the morning they demonstrated an altered circadian rhythm of plasma corticosterone (B) even under the normal light-dark cycle. The altered daily rhythm of plasma B consisted of two peaks, with one peak at 08.00 h in anticipation of meal feeding and a second peak corresponding to the normal peak of plasma B prior to lights-off seen in ad libitum-fed animals. Neither peak of plasma B in the meal-fed animals achieved the magnitude of the single peak observed in control animals. In spite of some quantitative differences during certain periods of the day, after the animals had adapted to meal feeding there was no difference in the basic profile of the daily rhythm of plasma immunoactive growth hormone (GH).

Effect of deprivation and time of refeeding on food intake

The amount of food eaten in a two hour trial by male Sprague Dawley rats was recorded after periods of food deprivation up to 42 hr in length. Rats ate 50-78% more when refed during the dark phase than when refed during the light phase. This occurred even when light fed animals were fasted for longer periods than the dark fed animals. Rats eat in a rhythmic pattern after deprivation. These data are in good agreement with data previously reported and extend it by increasing the number of observations, increasing the length of deprivation, and comparing different age groups.

The effect of liver denervation on meal patterns, body weight and body composition of rats

Neural liver glucoreceptors have been proposed as a primary controller of food intake (FI). Male Sprague-Dawley rats were either sham operated or liver denervated (LD). LD rats had all tissue cut between the liver and the esophagus, stomach and upper 1 cm of the duodenum. The hepatic artery and surrounding tissue were also removed. Finally the hepatic portal vein and the bile duct were stripped clean and the former phenol treated. Three days after surgery animals were placed in modules for continuous computer monitoring of feeding behavior. At no time after surgery did the daily food intake or body weight of the groups differ significantly. Meal size and frequency (light-dark distribution) were determined for 6 days and averaged. Neither parameter was altered by LD. During the next 6 months food intake and body weights of the groups did not differ significantly. At sacrifice, body composition was directly determined with no significant differences observed between LD and sham operated rats. LD were confirmed histologically. Monoamine histofluorescence of the livers of rats subjected to liver denervation revealed an absence of the normal fluorescence seen on small blood vessels in liver parenchyma of sham operated rats. The data do not support the concept that liver glucoreceptors are a major controller of FI.

Meal patterns of rats with dorsomedial hypothalamic nuclei lesions or sham operations

Rats with bilateral dorsomedial hypothalamic electrolytic lesions (DMNL rats) are hypophagic, hypodipsic and have reduced linear and ponderal growth when compared to sham operated controls (SCON). Nevertheless, previous studies have shown that DMNL rats eat and drink adequate amounts for their size and have normal body composition. In the present study we investigated meal parameters: meal size, and frequency (both light and dark period), total intake and meal size per metabolic size (body weight 0.75). Compared to SCON, DMNL rats at twelve days post surgery weighed less, were shorter, but had a normal body composition as determined by the Lee Index, and were hypophagic (grams eaten/day). The animals were placed into individual, self-contained feeding modules and given powdered chow. After familiarization to the modules, meal parameters were recorded continuously by a computer for an eight day period. While dark phase meal frequency did not differ significantly between groups, the lesioned rats took more meals during the light period. Over the eight-day measurement period DMNL rats were hypophagic compared to SCON in absolute terms. However, when total intake and meal size were normalized to metabolic size, these two parameters did not differ significantly between groups. Upon refeeding, after a one-day fast, the initial meal size of the normally hypophagic DMNL rats exceeded that of SCON. Rats with DMNL have previously been shown to have deficits in some hypothesized short-term food intake control mechanism (e.g., cholecystokinin, glucose sensing). Thus overeating by the lesioned rats after a fast could possibly result from a specific short term control deficit.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypophysectomy Alters the Diurnal Food Intake Patterns in Rats

Summary Hypophysectomy alters the normal diurnal feeding patterns of rats but on the average the hypophysectomized rats still consume the greatest percentage of their food during the dark phase. Compared to controls, hypophysectomized rats eat a similiar number of meals each day, however, the amount of food consumed and the duration of the meals are reduced. The pituitary gland seems to be one of the factors involved in sustaining the natural diurnal feeding rhythm in rats. The authors wish to thank Drs. Roger and Leung for the use of the food intake monitors, and we express our appreciation for the expert technical assistance of C. M. Friend, and to S. Turley for typing the manuscript.

The effect of intracerebroventricularly infused satietin on conditioned taste aversion and feeding in rats fasted different lengths

Satietin is a glycoprotein (50,000-70,000 daltons MW) found in human serum (greater than 2 micrograms/ml) that is reported to be a strong anorexigenic agent when infused (10-100 micrograms/rat) intracerebroventricularly (ICV) into rats. The initial three experiments presented here explored whether satietin suppresses food intake by making the animals ill or causing them to experience malaise. A two-bottle taste aversion paradigm was used for this testing. In all experiments the rats were fitted with chronic third ventricle cannulas. After recovery from surgery the rats were trained for at least 6 days to drink their water in one hour a day, 1100-1200-hr (LD12:12-hr, lights out 12:00-hr). In Experiment 1 and 3 satietin (100 or 25 micrograms/rat) or vehicle was infused ICV 30 minutes prior to exposure to a novel neutral preference fluid flavor (banana or almond flavoring in water). Three days later the rats were given a choice of the two flavors to consume; this was repeated the next day. In both experiments satietin treated rats showed strong aversion to the flavor paired with satietin infusion, while saline infused controls showed no aversion. A similar paradigm was used during the second experiment, except satietin or vehicle infusion was paired with a highly preferred saccharin-water solution. Three days later the rats were given a choice between water and the saccharin-water solution. The satietin (50 micrograms/rat) treated rats exhibited a marked aversion to the saccharin-water solution. These data suggest that satietin may be an aversive substance.(ABSTRACT TRUNCATED AT 250 WORDS)

Satietin: Fos mapping of putative brain sites of action

A purified extract of a blood-borne satiety factor, called satietin, was injected into the cerebral ventricles of rats that were either fed ad libitum or were food deprived. The animals were killed 2 h after injection and their brains subsequently sectioned and stained for Fos-like immunoreactivity (Fos-IR) to determine the putative sites of action for satietin in the brain. Fos-IR was induced in only a few locations, the most prominent sites being the bed nucleus of the stria terminalis, the central nucleus of the amygdala, and the parvocellular division of the paraventricular nucleus of the hypothalamus. Each of these areas has previously been implicated in the control of feeding behavior. Sites in the hindbrain that are associated with nausea were devoid of satietin-induced Fos-IR. Finally, these sites of action of satietin show some differences from sites that are prominently activated by other classes of anorectic agents.

Intracerebroventricular infusions of rat satietin into rats does not produce conditioned taste aversion

In a previous study we found that while human satietin (h-SAT) suppressed the food intake of rats it was also aversive to them. In the present study rat satietin (r-SAT) was tested for aversiveness in rats fitted with chronic third ventricle (ICV) cannulas. The rats were then given access to water for 1-hr/day and food ad lib for ten days. Fluid intake, food intake during fluid access and 24-hr total food consumption were recorded. The rats were then ICV infused with saline and 30 min later half of the animals given access to banana flavored water (Group 1) while the remainder were presented with almond flavored water (Group 2). The next day Group 1 was infused with saline and Group 2 with 100 micrograms/rat of r-SAT. Thirty minutes later the flavors presented to the rats were the reverse of the previous day. Satietin significantly reduced food intake during fluid access and for 24 hours. Thereafter, fluid and food ingestion of the groups was normal and similar. Thus no rebound feeding occurred in the r-SAT treated group. Two days after r-SAT or saline the rats were given a two-bottle choice test. Both groups displaced equal preference for the flavors, therefore r-SAT produced no taste aversion. The r-SAT treated rats lost more body weight than saline treated animals the first day after treatment. This difference increased the next day and remained significant for seven days post infusion, whereas, food consumption did not differ between the groups after the first day. The data indicate the food intake suppression in rats produced by r-SAT is not due to the compound being aversive.

Satietin: route of injection, dose response, effect on food and water intake and on running-wheel activity in the rat.

Semipurified satietin significantly (p less than 0.05) reduced food intake when injected subcutaneously at 10, 15, 20 mg/kg into 48 hr fasted rats with no indication of a dose response. When infused intracerebroventricularly (ICV) at 12.5, 25 and 50 micrograms/rat (10 microliter vol) into ad lib fed rats at the end of the light period there was no effect on food intake for the first hour but 24 hr food intake was (p less than 0.001) reduced at all doses. The ICV dose response curve was shallow, with similar suppression at both 12.5 and 25 micrograms doses, but a (p less than 0.05) greater suppression with the 50 micrograms dose. An ICV threshold between 6.25 micrograms and 12.5 micrograms appears to exist since no suppression occurred after a dose of 6.25 micrograms. Four consecutive daily ICV infusions of satietin (25 micrograms/rat) in two rats progressively suppressed food intake to low levels, suggesting a cumulative effect. Following termination of satietin treatment daily food intake slowly returned towards normal without evidence of rebound feeding. In other ad lib fed rats, four ICV infusions of semipurified satietin, on days alternated with no infusion, reduced food intake (p less than 0.001), water intake (p less than 0.003) and running wheel activity (p less than 0.001) on the first day of injection but not on subsequent injection days. Suppression of activity approached significance on the second injection day. Highly purified satietin infused ICV produced similar responses. These findings may indicate a general disruption of behavior by satietin, thus, it may not play a physiological role in feeding behavior because of its apparent non-specificity.

Hormone and Glucose Responses to Serial Cardiac Puncture in Rats

Summary Serial, apparently basal radio-immunoassayable plasma insulin and growth-hormone values were obtained when fast-knockdown ether anesthesia was used. Radioimmunoassayable prolactin was elevated at the second, third, and fourth bleedings but cause no apparent increase in circulating insulin levels. The elevation in plasma glucose may also have been a transient effect of sympathetic stimulation which simultaneously inhibited insulin release. The authors wish to thank Dr. H. H. Cole for his advice in preparing this manuscript. Also thanks are given to Mr. O. Lang and Mrs. R. Jund for technical assistance.