Biomedical subjects

V E Mendel

Publications and source records attributed to V E Mendel.

At least 19 recordsLinked to original sources

PubMed1996

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.

Amygdala↗

PubMed1995

Blood profile and balance study of rats given the putative anorectic agent satietin.

Satietin (SAT), a glycoprotein found in the plasma of a variety of animals, is a putative satiety agent. In experiments 1 and 2 rats received chronic third ventricle cannulas. At the start of the dark phase, in experiment 1, one group was infused with artificial cerebrospinal fluid (aCSF) and fed ad libitum (CON); a second group was infused with 100 micrograms/rat of human SAT and fed ad libitum in individual computerized pellet feeding modules; a third group was infused with aCSF and pair fed (PF) to the SAT-treated rats. The animals were killed 19.5 h later and blood was collected. Food and water intake and body weight were significantly, and comparably, reduced in the SAT-treated and PF group compared with the CON group. Plasma was assayed for a variety of nutrients, metabolites, enzymes, hormones, ions, and osmolality. Differential white cell counts were made. None of the above parameters differed significantly between the SAT and PF groups. Meal pattern analyses showed SAT treatment did not at any time alter meal size but significantly increased meal duration and intermeal interval during the first 6 h of the dark phase. In experiment 2 rats were placed in metabolic cages and infused with SAT or aCSF. Food and water intakes of the SAT group were suppressed for 1 day, whereas their body weights were significantly attenuated for 3 days. Urine volume and feces elimination were similar in the two groups over the 6-day measurement period. The normalcy of the data from experiment 1 is in accord with the possibility that SAT may act as a physiological satiety agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1994

Effects of components derived from HPLC purification of human satietin on ingestion, body weight, and taste aversion in the rat.

The putative satiety agent human satietin (h-SAT) once thought to be homogenous has been separated by high-performance liquid chromatography (HPLC) into components designated peak A (P-A, 53%/w) and Peak B (P-B, 47%/w); P-B contains a putative satiety agent. In Experiment 1, male Sprague-Dawley rats were divided into six (n = 9-11) groups (Grps) and ICV infused: Grp 1, artificial cerebrospinal fluid (a-CSF), 10 microliters/rat; Grp 2, albumin (ALB), 53 micrograms/rat; Grp 3, semipurified (sp) h-SAT (parent compound), 100 micrograms/rat; Grp 4, P-A, 53 micrograms/rat; Grp 5, P-B, 47 micrograms/rat; and Grp 6, P-A+B, 53+47 micrograms/rat, respectively. Compared to Grp 1, food intake, the first day postinfusion, was suppressed in Grp 3 (p < 0.01) and equally attenuated (p < 0.06) in Grps 5 and 6. Body weight remained suppressed (p < 0.05) in Grps 3, 5, and 6 for 3 days and in Grps 3 and 6 (p < 0.05) for an additional 3 days; Grps 2 and 4 did not differ from Grp 1. These data show P-B suppresses food intake comparably to P-A+B and causes a prolonged weight loss. In Experiment 2, sph-SAT and a recombination of P-A and P-B was tested for aversiveness using the two-bottle test. Both sph-SAT and P-A+B significantly suppressed food intake, but only sph-SAT was found to be aversive. These data show that most likely during HPLC processing of sph-SAT an aversive component was lost.

Angiotensin II↗

PubMed1991

HPLC-purified human satietin does not produce conditioned taste aversion in rats.

Human satietin is thought to be an endogenous glycoprotein that can suppress food intake and body weight. However, it was also found to be aversive when rats infused intracerebroventricularly (ICV) with human satietin were subjected to a two-bottle taste aversion test. More recently, the human satietin previously thought homogenous was separated by HPLC into two Peaks, denoted as A and B. In the present study, male Sprague-Dawley rats were fitted with chronic third ventricle cannulas and presented with fluid for 1 h/day, while food was given ad lib. After training, the rats were ICV infused with either artificial cerebrospinal fluid, Peak A or Peak B of human satietin. Peak B significantly reduced short-term and 24-h food intake, whereas their fluid intake was nonsignificantly attenuated. Peak A had no affect on either food or fluid intake on the day it was administered. When the rats were given the two-bottle taste aversion test neither compound was found to be aversive. These data suggest that Peak B may contain satietin(s) which could be a candidate for an endogenous satiety agent.

Animals↗

PubMed1991

Interaction of cholecystokinin-8 and pancreatic glucagon in control of food intake in dogs.

Feeding responses to continuous intravenous administration of graded doses of the COOH-terminal octapeptide of cholecystokinin (CCK-8) and pancreatic glucagon, alone and in combination, were determined in dogs fasted 4 h. Low doses of glucagon (50, 500, 5,000, 6,000 pmol.kg-1.h-1) had no effect on food intake, whereas higher doses (12 and 24 nmol.kg-1.h-1) depressed intake by 50-60%. Of the CCK-8 doses administered (50 and 400 pmol.kg-1.h-1), food intake was depressed only at the higher dose (53%). This effect was blocked by glucagon (50-5,000 pmol.kg-1.h-1). Simultaneous administration of 50 or 500 pmol.kg-1.h-1 of glucagon and 50 pmol.kg-1.h-1 of CCK-8, doses currently thought to produce plasma peptide levels similar to those occurring postprandially in dogs, had no effect on food intake. These results suggest that plasma levels of CCK and glucagon after a meal are not sufficient alone or in combination to produce satiety.

Animals↗

PubMed1990

The effects of semi- and HPLC-purified human satietin and alpha-1-glycoprotein on ingestion and body weight.

Satietin is thought to be an endogenous glycoprotein that can suppress food intake (FI) and body weight (b.wt.). In Experiment 1, rats were ICV infused with either a-CSF or with 50 micrograms/rat of human satietin. FI was suppressed (p less than 0.05) for 2 days after infusion, whereas b.wt. was attenuated (p less than 0.05) for 14 days. In Experiment 2, the previously thought homogenous human satietin was further purified by HPLC and this yielded two peaks (A and B). Rats were ICV infused with either a-CSF or 50 micrograms/rat of Peak A, Peak B or the semipurified parent human satietin (sph-SAT) from which the peaks were derived. All three treatments suppressed (p less than 0.05) FI on day 1 after infusion and on day 2 in the groups that received Peak A and sph-SAT. Body weight was attenuated (p less than 0.01) in all the experimental groups on day 1 and for 2 and 10 days, respectively, in the Peak A and sph-SAT-treated groups. Immunostaining revealed Peak A contained both albumin and alpha-1-glycoprotein (A1G), whereas Peak B contained neither. In the last experiment rats were ICV infused with either a-CSF or 50 micrograms/rat of A1G or A1G that was put through the sph-SAT extraction procedure. FI was suppressed (p less than 0.01) and b.wt. attenuated in both experimental groups only on the first day postinfusion. These data suggest that some, but possibly not all, of the previously found biological activity attributed to sph-SAT might be due to contaminants of the preparation.

Albumins↗

PubMed1989

Interaction of CCK-8 and somatostatin-14 in control of food intake in dogs.

interactions of cholecystokinin COOH-terminal octapeptide (CCK-8) and somatostatin-14 (SS-14) on food intake in dogs were examined by administration of graded doses of these peptides alone and in combination. In animals fasted 19 h, SS-14 (2,000 or 20,000 pmol.kg-1.h-1) had no effect on food intake. In animals fasted 4 h, food intake was not affected by 40 or 400 pmol.kg-1.h-1 SS-14 but was significantly (P less than 0.05) increased by 20% after 4,000 pmol.kg-1.h-1 SS-14. Feeding responses to simultaneous infusions of CCK-8 (50 or 400 pmol.kg-1.h-1) and SS-14 (40, 400, or 4,000 pmol.kg-1.h-1) were determined in animals fasted 4 h. Given alone, the high dose of CCK-8 (400 pmol.kg-1.h-1) significantly (P less than 0.01) depressed food intake by 55%. This effect was blocked by all doses of SS-14. In the absence of CCK-8, SS-14 had no effect except at the highest dose (4,000 pmol.kg-1.h-1), which significantly (P less than 0.01) stimulated food intake by 57%. This effect was blocked by both doses of CCK-8. Simultaneous infusion of lower doses of SS-14 (40 and 400 pmol.kg-1.h-1) and CCK-8 (50 pmol.kg-1.h-1) had no effect on food intake. These results suggest that plasma levels of CCK and SS-14 after a meal are not sufficient alone or in combination to produce satiety.

Animals↗

PubMed1988

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.

Animals↗

PubMed1988

Human satietin: rapid development of tolerance and its specificity to feeding behavior in rats.

Semipurified human satietin (SP hSAT) significantly (p less than 0.05) reduced food intake for each of five consecutive days when injected intraperitoneally (2 mg/kg/day). Tolerance developed rapidly during the second and third days of injection but food intake of those animals receiving the highest doses of Sp hSAT (1 and 2 mg/kg/day) remained significantly below (p less than 0.05) that of the saline-injected animals. Food intake of rats receiving doses of 0.5 and 0.25 mg/kg/day Sp hSAT was below that of the saline-treated group for the first two days of injection (p less than 0.05) but not thereafter. Water intake fell in all satietin-treated groups on the first day of injection, thereafter, it was similar to the saline-treated group. In a second study Sp hSAT (1, 0.5, 0.25 mg/kg/day) was continuously infused IP by Alzet pumps. All doses of Sp hSAT significantly reduced food intake below that of the saline-treated group for the entire 7 days of infusion (p less than 0.05); water was not affected except on the first day of infusion (p greater than 0.01). In a third study, injection of purified human satietin (p hSAT) (2 mg/kg, IP) in fasted rats (24 hr) had no effect on water consumption either during fast or 24 hr postfast (p greater than 0.05). In a fourth study p hSAT was continuously heated to 37 degrees C. Aliquots were taken each day and injected (IP) into 4 naive rats (total of 24 rats) for a total of 6 days of heating (120 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Pyrrolizidine alkaloid-induced liver disease in horses: an early diagnosis.

Nine adult horses were fed alfalfa hay cubes containing approximately 10% Senecio vulgaris until all horses had consumed approximately the same amount of toxic components of S vulgaris, pyrrolizidine alkaloids (PA). The amount of PA consumed was determined by the amount that induced clinical signs of PA toxicosis in 3 horses. The 6 other horses were given similar amounts per kilogram of body weight. An initial decrease of feed intake was observed when horses' diets were changed from alfalfa cubes to alfalfa/Senecio cubes, and feed intake was decreased further over 89 to 98 days. From 50 to 159 days, body weight decreased in all horses. Liver disease was induced in all 9 horses after they ate an average of 233 +/- 9.2 mg of PA/kg of body weight. Eight horses died or were euthanatized. Treatment with branched chain amino acids had no effect on mortality, but appeared to reduce neurologic problems. Clinical signs of PA-induced liver disease included ataxia, head pressing, and decreased feed intake. Other clinical signs of toxicosis were observed individual horses, but did not develop in most horses. Megalocytic hepatopathy developed. Liver abnormalities proceeded as PA was consumed and were severe in 8 of 9 horses before clinical signs of toxicosis appeared. Sulfobromophthalein sodium clearance did not decrease until PA-induced liver disease was advanced. Bile acid (BA) concentrations increased to greater than or equal to 50 mumol/L, in the 8 horses that died. One horse had hepatopathy and increased BA concentration, but survived. In this horse, BA concentration peaked at 33 mumol/L and then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Branched-Chain↗

PubMed1987

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.

Animals↗

PubMed1987

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↗

PubMed1986

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)

Animals↗

PubMed1986

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↗

PubMed1986

Clinicopathologic study of horses surviving pyrrolizidine alkaloid (Senecio vulgaris) toxicosis.

Twenty horses of various ages had inadvertently ingested alfalfa hay contaminated with Senecio vulgaris. Among them, 4 died of liver disease. Blood was collected from affected horses at monthly intervals for 7 months and at the 9th and 14th months. The following serum enzymes and chemical items were assayed: aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transferase, sorbitol dehydrogenase, total bilirubin, BUN, glucose, cholesterol, inorganic phosphate, calcium, total protein, and albumin. Amino acid profiles, conjugated bile acids, sulfobromophthalein clearance times, and liver histopathologic changes via serial biopsies were also monitored. Liver histopathologic changes revealed lesions progressively increasing in severity. Aspartate aminotransferase and plasma amino acid ratios indicated chronic liver degeneration (0.05 level of significance). gamma-Glutamyl transferase and lactate dehydrogenase as well as BUN values fluctuated, but returned to within reference values. Horses appeared clinically normal 14 months after intoxication, but were unable to tolerate stress of exercise.

Amino Acids↗

PubMed1985

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↗

PubMed1984

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↗

PubMed1984

Effects of glucagon, insulin, propionate, acetate, and HCO3 on K excretion in sheep.

The effects on renal K excretion of 1 h intravenous infusion of glucagon, insulin, Na propionate, Na acetate, or NaHCO3 were studied in mature, conscious fasted ewes. These treatments were compared with the fasted state without treatment (control) and with feeding a single daily meal. Renal K excretion was increased by feeding and by Na propionate and Na acetate treatments but not by infusion of glucagon, insulin, and NaHCO3. Since hormone levels were elevated more by specific hormone infusions than by feeding or Na propionate infusions, these results do not support a role for glucagon and insulin in mediating the increases in renal K excretion that occurred after meals or during acetate and propionate infusions. The mechanisms responsible for the acetate- and propionate-induced kaliuresis are not clear but do not appear to include changes in plasma K (PK), glucagon, and insulin (Pinsulin) or in urine flow and urine Na excretion. However, a relation between insulin and K was observed during infusion of KCl in fasting sheep. Above a PK threshold of 4 meq/l, Pinsulin (ng/ml) = 1.52 PK (meq/l) - 5.89. In other experiments, K excretion increased after an intravenous bolus injection of 1 mg of glucagon, indicating that sheep, like humans and dogs, respond to pharmacologic doses of glucagon with kaliuresis.

Acetates↗