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L L Bellinger

Publications and source records attributed to L L Bellinger.

At least 55 records · Page 3Linked to original sources

Normal catch-up growth in rats severely food-restricted prior to lesions of the dorsomedial hypothalamic nucleus: the first 48 hours.

Following a brief period of ad lib (AL) feeding, 45-day-old male Sprague-Dawley rats were either fed AL or food-restricted (REST) for 21 days to 50% of the intake of the AL rats. At this time, some AL and some REST rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL), whereas other AL and REST rats were sham-operated (CON). Following this, all rats were refed (REF) AL and killed two days later. At this time, DMNL-REST + REF and DMNL-AL weighed as much as CON-REST + REF and CON-AL, whereas the body weight of the DMNL-AL group began to separate from the CON-AL group; carcass lipid and protein were normal among the groups. DMNL-AL laid down more % lipid and % protein/g food eaten than CON-AL; this was not the case in the REST + REF groups. DMNL-AL were hypophagic vs. CON-AL, but DMNL-REST + REF ate as much as CON-REST + REF. Compared to DMNL-AL, DMNL-REST + REF increased their food intake more than four-fold and also utilized food energy more efficiently than DMNL-AL rats. Epididymal fat pads and kidneys were smaller in REST + REF vs. AL groups, irrespective of brain manipulation. Plasma glucose and growth hormone were normal among the groups, but plasma insulin concentrations were higher in REST + REF DMNL and CON groups vs. DMNL-AL and CON-AL, respectively. Glucose incorporation into epididymal fat pad lipid and CO2 and liver lipid was elevated in REST-REF groups vs. respective AL groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of liver denervation on the consumption of various diets by rats.

Liver afferents have been proposed to influence food intake control, however, previous studies have shown that chow (pellet) intake is apparently not altered in total liver denervated rats. The present study explored whether total liver denervation could alter the rats' intake of various diets other than chow pellets. Total liver denervations were verified using staining histological and monoamine histofluorescence techniques. The denervated and sham operated rats were given short-term (4-6 days) exposure to four diets: (diet 1, chow plus a 32% w/v sucrose-water solution; diet 2, 1:1 mixture of powdered chow and granular glucose; diet 3, 33% w/w Crisco and powdered chow mixture and diet 4, a 5% w/v glucose-water solution plus chow. Body weight gains were not affected-by either surgery or diet exposure. Daily consumptions of the diets were similar in both groups, nevertheless, there was a trend for the denervated rats to consume slightly more of a high fat diet, which lends support for one hypothesized liver satiety mechanism. Also, the denervated rats consumed less (an average 5 kcal/day) of the 5% glucose solution (one hypothesis tested would predict an increase consumption of glucose by the denervated rats). Thus the liver may play a role, albeit small, through several ill defined mechanism(s) in the regulation of feeding.

Afferent Pathways↗

Ingestion, body weight and activity of rats receiving repeated intracerebroventricular infusions of rat satietin.

Satietin is a putative satiety agent that is found in a variety of species including man and the rat. In the first experiment male Sprague-Dawley rats were fitted with chronic third ventricle cannulas and placed in activity wheels. After recovery, animals were intracerebroventricularly (ICV) infused with either sterile rat satietin (r-SAT) (100 micrograms/rat) dissolved in 10 microliters saline (n = 6) or sterile saline (n = 8). Infusions were repeated the next two days. Infusions of r-SAT had no effect on the rats' water intake or activity but did suppress (p less than 0.05) their food consumption when compared to the controls, but only after the first and second infusions. Thus tolerance to r-SAT quickly developed using this schedule of administration. Notably, body weight of the r-SAT infused rats remained attenuated (p less than 0.01) for four days following the first infusion. In the second experiment the rats were ICV infused every fourth day with either r-SAT (100 micrograms/rat) (n = 10) or saline (n = 8) for a total of three infusions. Food, but not water, intake was significantly suppressed after the first and second infusions and lowered nonsignificantly after the third. Body weight was significantly reduced after the first r-SAT infusion and remained statistically reduced for seven days after the third infusion; at a time when the rats' food intake was normal. These data suggest that in addition to a r-SAT suppression of feeding, other r-SAT induced changes (possibly metabolic) may help reduce the rats' body weight. The above dose of r-SAT had no affect on the animals' rectal temperature. The data of the above two experiments reveal that r-SAT infused ICV into rats can suppress the animals' food intake and lead to a prolonged attenuation of body weight.

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Further evidence for the existence of an "organismic" set point in rats with dorsomedial hypothalamic nucleus lesions (DMNL rats): normal catch-up growth.

The present study was performed to assess the capacity of rats with dorsomedial hypothalamic nucleus lesions (DMNL rats) and sham-operated controls (CON) for catch-up growth following body weight (b.wt.) reduction prior to DMNL (and sham-lesion) production. Male SD rats (45 days, 157 +/- 1.3 g) were maintained for 11 days ad lib (ADLIB) after arrival and then divided into two groups. One group continued to feed ADLIB, the other group was fed half of the ration eaten by ADLIB rats for 32 days. At this point each group was divided into two subgroups. One subgroup received DMNL, the other subgroup consisted of CON. From then on all rats were fed ADLIB [except for one group of CON that was pair-fed to the ADLIB DMNL rats (PF-CON)] for 37 days (69th day of experiment) and then killed. DMNL rats lesioned at normal b.wt. (ADLIB DMNL) showed a precipitous drop in food intake, b.wt. and efficiency of food utilization (EFU). In striking contrast, rats that had received DMNL after b.wt. restriction (REST DMNL) and were then refed ADLIB showed a dramatic rise in food intake, b.wt., change in b.wt. and EFU, the latter being almost twice that of the ADLIB DMNL. Notably, the PF-CON weighed less than the ADLIB CON and utilized food poorer than ADLIB CON, REST CON and ADLIB DMNL. Liver weight (both absolute and relative (per kg 3/4 b.wt.) was reduced in DMNL irrespective of dietary treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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Capsaicin and its effects upon meal patterns, and glucagon and epinephrine suppression of food intake.

The neurotoxin capsaicin has been shown to selectively interfere with unmyelinated sensory fibers, as well as leading to depletions of substance P and other peptides. Meal pattern analysis was performed both before and after treatment with capsaicin in twelve adult male Sprague-Dawley rats. Capsaicin treatment only briefly altered feeding patterns. No long term effect on body weight was noted. These same animals were then tested for the appetite suppressing effects of IP injections of glucagon (125 micrograms/kg) and epinephrine (30 micrograms/kg). Capsaicin treated rats decreased their intake of sweetened condensed milk during a 30 minute test in response to glucagon and epinephrine. Controls failed to suppress intake in response to glucagon, but drank less milk after epinephrine than did capsaicin treated rats. Efficacy of capsaicin treatment was obtained using similarly treated animals subject to histological evaluation within 2 days of capsaicin treatment. These results suggest that peripherally generated information relayed to the CNS via small-diameter sensory neurons is not a necessary component of the normal hunger/satiety sequence, nor body weight regulation.

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The effect of continuous intracerebroventricular infusion of satietin on ingestion, activity and body weight of rats.

Satietin is a putative satiety agent when given either peripherally or intracerebroventricularly (ICV). In the present study male Sprague Dawley rats were fitted with chronic third ventricle cannulas. After recovery, Alzet seven day osmotic pumps were inserted subcutaneously and tubing was connected to the cannula. Rats were then infused ICV with saline or semi-purified human satietin (25 micrograms/day; 1 microliter/hr). In the satietin group, daily chow intake was reduced (p less than 0.05) on days 1 and 2, recovered to control levels on days 4 and 5 and again declined (p less than 0.05) on days 6-8. During this latter period the satietin treated animals appeared ill. The satietin group's water intake paralleled food consumption, whereas the groups' water/food intake ratios did not differ. Satietin infusions decreased (p less than 0.01) the rats' body weight 42 grams by day 4, whereas the control group's weight remained constant. Even during the period where the satietin group's food intake returned to control levels they continued to lose weight. Running wheel activity was reduced throughout the satietin infusion period even when food and water ingestion had returned to control levels. The data suggest that semi-purified human satietin, when tested in rats, is an anorexogenic agent, however, its continuous use quickly produces tolerance and later what may be a cross-species allergic reaction (due to the satietin itself or a contaminant). The appropriateness of testing semi-purified satietin in the rat model is questioned.

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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.

Animals↗

Ingestive behavior of rats with ibotenic acid lesions of the dorsomedial hypothalamus.

Rats with electrolytic or kainic acid (KA) lesions of the dorsomedial hypothalamic nucleus area (DMHA-L) are hypophagic, hypodipsic, and have a reduced body weight (BW) compared with controls. In the present study, male Sprague-Dawley rats received bilateral ibotenic acid (IBO) lesions of the DMHA (3 micrograms in 0.3 microliter) or sham (S) operations. During the next 32 days the IBO DMHA-L rats showed reduced (P less than 0.01) food and water intake, BW, and linear growth (P less than 0.03), although having a normal Lee obesity index. After a 24-h fast both groups became hyperphagic (P less than 0.01) with the DMHA-L group eating the most (P less than 0.01) during the 1st h; lost BW was regained at the same rate. In the absence of food, DMHA-L rats took less (P less than 0.01) water (data normalized) than S rats. During 24 h of water deprivation, both groups ate similar amounts of food (data normalized); following deprivation the groups were hyperdipsic. Both groups increased their food intake when given 300 mg/kg of 2-deoxy-D-glucose, which contrasts rats with electrolytic or KA DMHA-L rats. Both groups decreased their food intake when given cholecystokinin (3 micrograms/kg ip), which contrasts rats with electrolytic DMHA-L. The DMHA-L rats were not deficient in plasma glucose, insulin, growth hormone, or plasma Na+ and K+. Histology revealed many, but not all neurons, were destroyed in the DMN after IBO. The data indicate that IBO, electrolytic, or KA lesions of the DMHA produce similar but not identical physiological changes.

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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)

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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.

Animals↗

Liquid sucrose and fructose intake in male and female liver denervated rats.

Male and female rats were liver denervated [hepatic vagal branch transection (VAG-B), hepatic artery-portal vein denervations (H-ART) or total liver denervation (TOTAL)] and sham operated (SHAM). Rats were given chow along with exposure to sucrose and fructose solutions. Chow intakes and body weight gains of all experimental groups were similar to their SHAMS, but the male H-ART group weighed more than the male VAG-B group. Denervated male and female rats consumed amounts of 30% sucrose solution similar to their SHAMS; however, the female H-ART group took more than the female TOTAL rats. Female VAG-B and male H-ART groups drank more of a 30% fructose solution than their other groups. Mean 15% fructose intakes, for both sexes, of denervated rats were similar to their SHAMS. The data are not supportive for a role of liver satiety afferents in fructose and sucrose intake but do raise the possibility that autonomic nervous system balance to the liver could influence the rats' ingestion of these sugars. If true, the mechanism(s) must be generally subtle and somewhat sex variable.

Animals↗

Effect of palatable diet on growth, caloric intake and endocrine-metabolic profile in weanling rats with dorsomedial hypothalamic lesions.

Weanling male Sprague-Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated rats served as controls. All animals were fed lab chow for 15 postoperative days. At that time they were subdivided into two groups each. One DMNL and one control group continued to be fed lab chow until the termination of the experiment on postoperative day 116. A second DMNL and control group were fed a high-fat diet and 32% sucrose solution (HF/SS diet). All DMNL rats showed reduced body weight and linear growth, but the HF/SS diet depressed these parameters further below the levels of the chow-fed groups. Both DMNL and control rats fed HF/SS had more carcass fat, heavier epididymal fat pads, more carcass fat per calories eaten, higher plasma levels of glucose, glycerol and free fatty acids but lower insulin levels than chow-fed DMNL rats and controls. This occurred in the face of lower body weights and caloric intake. Neither growth hormone nor insulin showed lesion effects. Rats with DMNL exhibited the same inverse relationship between plasma insulin and free fatty acids as controls. The data indicate that DMNL rats respond to the HF/SS diet essentially like sham-operated controls, i.e., they develop dietary obesity. Although they do show some small deficits, their lipogenic capacity is actually significantly greater than that of HF/SS-diet fed controls.

Animals↗

Glucagon and epinephrine suppression of food intake in liver-denervated rats.

Milk intake suppression after intraperitoneal glucagon and epinephrine injections was studied in liver-denervated [hepatic vagal branch transection (VAG-B), hepatic artery-portal vein denervations (H-ART), or total denervation (TOTAL)] and sham-operated rats (SHAM). In experiment 1, glucagon (500 micrograms/kg, Sigma) had no effect on 30 min of milk intake but produced hyperglycemia in all groups. Glucagon (750 micrograms/kg, Sigma; 400 micrograms/kg, Lilly) decreased intake in all groups, as did epinephrine (30 micrograms/kg). In experiment 2, TOTAL and SHAM were tested with 50, 100, and 400 micrograms/kg of glucagon (Lilly). Only the two larger doses suppressed milk intake of both groups, whereas all doses caused hyperglycemia. Epinephrine (30 micrograms/kg) decreased food intake more than glucagon but caused less hyperglycemia than any glucagon dose. In experiment 3, VAG-B and SHAM groups were given glucagon (400 micrograms/kg, Lilly), which reduced their intake. Under these test conditions, liver innervation is not required for glucagon and epinephrine to suppress milk intake. The ability of the two hormones to suppress ingestion appears to be dissociated from their hyperglycemic actions.

Animals↗

Plasma hormone levels in growth-retarded rats with dorsomedial hypothalamic lesions.

Rats with lesions in the dorsomedial hypothalamic nuclei (DMNL rats) are hypophagic and growth-retarded. Since previous work had shown normal plasma growth hormone and insulin levels in DMNL rats we investigated the diurnal patterns of these and other hormones involved in growth. Trial 1: Rats received electrolytic DMNL or sham operations (SCON). The DMNL rats exhibited no differences from SCON rats in plasma triiodothyronine (T3), growth hormone (GH), insulin and somatomedin (SM) concentrations, Trial 2: kainic acid, a neurotoxin, was used for lesion production. Again, DMNL rats showed no deficiencies in plasma levels of T3, GH or insulin. Trial 3: In this experiment, diurnal hormone profiles were assessed. The GH profile and mean 24-hour secretion of both DMNL and SCON groups did not differ significantly. Both groups exhibited a diurnal release of T3, with the DMNL rats showing slightly higher levels. Plasma insulin rose after dark, i.e., at the onset of feeding, in SCON but not in DMNL rats; the later have a previously reported disrupted feeding rhythm. Glucose patterns were in keeping with insulin profiles. Controls showed a normal plasma corticosterone rhythm whereas DMNL rats had an altered pattern. The data suggest that deficiencies in the principal anabolic and growth-promoting hormones cannot be responsible for the retarded growth of DMNL rats.

Animals↗

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)

Animals↗

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.

Animals↗

Suppressive effects of naloxone on food and water intake in vagotomized rats.

Rats were (1) sham operated and ad lib fed, (2) given bilateral subdiaphragmatic vagotomies or (3) sham operated and pair fed to the vagotomized group. At the start of the dark period, following a 24 hr fast, the animals were tested for the ability of naloxone (0.5, 1.5, 3.0 and 5.0 mg/kg body weight) to suppress food and water consumption. In comparison to saline control injections the data indicated that naloxone was equally effective in suppressing food intake, over a two hour period, in all groups. Similarly naloxone effectively decreased water consumption of all groups in comparison to their saline trials. When the post naloxone data were calculated as a percentage of saline baseline this suppression was, at times, slightly greater in the vagotomized group than in the other groups. However, this may be an artifact of the low baseline intake of the vagotomized group. The results are discussed with relevance to the recent findings of others concerning this subject.

Animals↗