Effect of gonadectomy on taste preference for glucose solutions in rats.

Mature male and female rats maintained on an ad lib diet were given a choice between tap water and glucose solutions of different concentrations (1, 5 and 12 percent). Both sexes exhibited a definite preference for the 12 percent glucose solution, but the females drank significantly more than males. Gonadectomy produced neither quantitative nor qualitative changes in the choice made by male rats. On the contrary, gonadectomized females showed a depression of the 12 percent glucose solution intake and an increase in the 5 percent glucose solution intake, resulting in a decrease of the total fluid intake. A comparison of ovariectomized and intact female rats in regard to the self-selection of tap water and a 5 percent glucose solution confirmed the stimulatory effect of ovariectomy on the 5 percent glucose solution intake. When a choice between tap water and 12 percent glucose solution was permitted the ovariectomized rats showed a weaker positive response to the sweet solution than the intact female rats.     

Some determinants of intake of glucose+saccharin solutions

In the present three experiments, tests were run to see if postingestional factors played a role in the excessive drinking elicited by the combination of 3% glucose and 0.125% saccharin solutions. The first experiment showed a marked increase in the total daily caloric intake and a decrease in the proportion of calories taken from the food when the glucose+saccharin (G+S) solution was presented to rats. In spite of this alteration of diet induced by G+S drinking, Experiment 2, which compared the drinking of various concentrations of glucose solutions and G+S solutions, demonstrated that the rat drinks these large quantities of the G+S solution for taste, not calories. The final experiment compared preference tests on various concentrations of saccharin, glucose or G+S solutions and showed that preference data across concentrations of G+S were qualitatively similar to the saccharin preference data, and different from the glucose data, even though it was the amount of glucose in the concentrations that was manipulated.     

Note on sex difference, early experience and food intake in rats

Rats which received either preweaning or postweaning stimulation were compared with controls for 11 days on a 10 min feeding test. The results indicated that although males consumed more wet mash than females, the nonstimulated controls ate as much as did rats in the two experimental groups. When body weight differences between the sexes were taken into account in the analysis, the food consumption of female rats was found to be equivalent to that of males.     

Taste responses to dilute sucrose solutions are modulated by stage of the estrous cycle and fenfluramine treatment in female rats

Meal size is decreased during the estrous stage of the rat's ovarian reproductive cycle. This is mediated, in part, by estradiol's ability to increase the strength by which negative-feedback signals function to inhibit meal size. For example, we recently reported that the anorectic effect of fenfluramine, a serotonin agonist, is enhanced during estrus. Here, we investigated whether a decrease in the strength of positive-feedback signals, like those related to the taste of food, contributes to the decrease in meal size observed either in estrous rats or following fenfluramine treatment. Rats were given brief access to six sucrose solutions (0.0, 0.025, 0.05, 0.1, 0.2, and 0.4 M) and the mean number of licks to these solutions was monitored in diestrous and estrous rats treated with 1 mg/kg fenfluramine or saline vehicle. Following saline treatment, estrous rats displayed fewer licks than diestrous rats to the 0.025 M sucrose solution. Following fenfluramine treatment, a decrease in the number of licks to 3 of the 5 sucrose solutions was observed in diestrous rats only. This decrease in sucrose palatability was limited to brief access tests, as overnight preference for the 0.025 M sucrose solution was not decreased by fenfluramine in either diestrous or estrous rats. Our findings suggest that estrous rats experience a decrease in the strength of positive-feedback signals elicited by a dilute sucrose solution and that the anorectic effect of fenfluramine is associated with a decline in positive-feedback signaling in the diestrous rat.     

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

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

Effect of diet consistency, taste and calories on food intake of weanling rats with dorsomedial hypothalamic lesions

Male weanling Sprague-Dawley rats with dorsomedial hypothalamic lesions (DMNL rats) primarily destroying the dorosomedial hypothalamic nuclei (DMN) showed significant hypophagia on lab chow chunks compared to sham-operated controls. When given a choice between lab chow in the form of chunks or powder, both controls and DMNL rats ate similar amounts of lab chow powder while DMNL rats ate less lab chow chunks. Total caloric consumption was the same as on chunks alone. When returned to lab chow chunks as the only source of calories, the pattern and magnitude of intake was again depressed for the DMNL rats. When offered a choice between Ginger Snaps cookies in chunk form versus powder, DMNL rats remained hypophagic in terms of chunk consumption while the intake from powder was similar in both controls and DMNL rats. When offered a choice between chunks of lab chow and Ginger Snaps, DMNL rats were again hypophagic on lab chow chunks, ate the same as the controls of the cookies, and the total caloric intake was of the same magnitude and pattern as observed in previous tests. The data suggest, but do not conclusively show, that DMNL rats are not hypophagic because they have an aversion to chewing hard food and that, when offered a diet similar in hardness to lab chow chunks i.e., hard cookies, will prefer the less tasty but nutritionally complete lab chow. They are apparently capable of choosing a diet for complete nutrition and, as previously reported, can meter calories competently.     

Serum insulin,glucose and triglyceride responses of Zucker obese and lean rats to cholecystokinin

Zucker obese rats are less sensitive to cholecystokinin (CCK), a putative satiety agent which also stimulates insulin and glucagon release. Changes in serum insulin, glucose and triglycerides, which are elevated in the obese rat, were compared with those in lean rats after saline and CCK-8 injection in fed and non-fed rats. Serum insulin increased 15 min after injection of CCK-8 in both lean and obese rats. In lean rats only, insulin subsequently decreased in both fed and non-fed rats. In both lean and obese rats injected with CCK-8 serum glucose did not change with feeding and was less than in saline-injected rats. While triglyceride concentrations were unaffected by either treatment in lean rats, in obese rats they were increased 100% 15 min after injection of CCK-8 and subsequently decreased in both fed and non-fed rats. Thus, CCK-8 elicited changes which were different from those which occur during normal feeding. Increased serum insulin, glucose and triglycerides which occurred 15 min after injection of saline only in obese rats may be due to increased susceptibility to the stress of being injected and may account for the decreased satiety effect of CCK-8.     

Effects of glucose and saccharine solutions on subsequent food consumption

Twenty three hr water deprived animals were given access to various glucose and glucose + saccharin solutions during a 1 hr drinking session. Subsequent 1 hr and 22 hr food intakes were measured. Results indicate that more food was consumed during the first post drinking hour by the animals when receiving 3.5% GLU + 0.25% SACC while comparatively less food was consumed by them following the ingestion of 21% GLU and 21% GLU + 0.25% SACC. During the remaining 22 hr when the animals received 21% GLU and 21% GLU + 0.25% SACC they increased their food intake such that total 23 hr food intake was unaffected. Food intake was not related to the amounts of the different fluids consumed but appeared to be determined by other oral and post ingestion factors associated with the different solutions.     

Effects of insulin on food intake and plasma glucose level in fat-fed diabetic rats

Schedules of insulin treatment which reliably increased eating in fat-fed diabetic rats were studied for their effect on plasma glucose concentrations. An inverse correlation between intake and plasma glucose was observed in fat-fed diabetics given long-term treatment with protamine-zinc insulin (PZI); however changes in glucose did not account for the differential effect of insulin on food intakes in normal controls or normal and diabetic rats fed a low-fat food. A single injection of 1 U PZI which increased eating in fat-fed diabetics but not normal controls 17–23 hr later did not reduce glucose concentrations from hyperglycemic levels in diabetics during the same time period. Injections of regular insulin increased eating in fat-fed diabetic and normal rats in a comparable fashion, but did not reduce plasma glucose in diabetics as low as in normal animals. The results show that the effect of exogenously administered insulin on food intake in fat-fed diabetics is largely unrelated to changes in circulating glucose levels and suggest that metabolic consequences of insulin treatment other than hypoglycemia may underlie the effect of the hormone on feeding in these animals.     

清醒大鼠胰岛素钳夹术及其糖代谢变化

为准确地评价在体组织对胰岛素 (Ins)的敏感性及探讨在胰岛素抵抗 (IR)状态下机体糖代谢变化。采用 6 ,6 D2 葡萄糖作为示踪剂 ,建立了自由状态下大鼠正常血糖 -高胰岛素钳夹术 ,并动态观察了其体内糖代谢的动态改变及血浆游离脂肪酸 (FFA)和Ins浓度随时间变化的过程。大鼠在 4 8mU (kg·min)速率Ins输注下 ,血糖稳定在正常水平而肝糖输出被抑制 ,胰岛素介导的机体葡萄糖利用率较基础状态显著增加 ,游离脂肪酸 (FFA)浓度显著下降。本钳夹术平均血糖变异系数为 5 76 %。平均GIR变异系数为 6 2 5 % ,GRd为 9 17%。重复试验GIR与GRd误差范围为 1 2 %和 1 7%。以 6 ,6 D2 葡萄糖作为示踪剂建立的自由状态下的大鼠正常血糖钳夹技术具有准确、可靠 ,无放射污染等优点 ,在外源性胰岛素 -葡萄糖代谢稳定状态下 ,机体对葡萄糖利用显著增加 ,脂肪分解显著减少。     

48-h glucose infusion in humans: effect on hormonal responses, hunger and food intake

Experimentally-induced hyperglycemia by prolonged glucose infusion allows investigation of the effects of sustained stimulation of the pancreatic β-cell on insulin secretion and sensitivity. Hormonal responses to a meal following prolonged glucose infusions have not been investigated. To determine if a 48-h glucose infusion alters hormonal responses to a test meal as well as food intake and hunger in normal weight individuals, 16 subjects (8 men, 8 women, age 18–30 years, mean BMI = 21.7 ± 1.6 kg/m²) were infused for 48 h with either saline (50 ml/h) or 15% glucose (200 mg/m²/min). Subjects ingested a 600 kcal mixed nutrient meal 3 h after infusion termination. Blood samples were taken during the 48 h and for 4 h following food ingestion. The 48-h glucose infusion elicited a metabolic profile of a glucose intolerant obese subjects, with increased plasma glucose, insulin and leptin (all P < 0.01) and increased HOMA-IR (P < 0.001). During meal ingestion, early insulin secretion was increased (P < 0.05) but post-prandial glucose (P < 0.01) and insulin (P < 0.01) excursions were lower following the glucose infusion. Post-prandial plasma triglyceride concentrations were increased after glucose compared with saline. Food intake and hunger ratings were not different between the two conditions. Plasma leptin levels were inversely correlated with hunger (P < 0.03) in both conditions and with food intake (P < 0.003) during the glucose condition only. Thus, a 48-h glucose infusion does not impair post-prandial hormonal responses, alter food intake or hunger in normal weight subjects. The glucose-induced increases in plasma leptin result in a stronger inverse relationship between plasma leptin and hunger as well as food intake. These data are the first to demonstrate a relationship between leptin and hunger in normal weight, non-calorically restricted human subjects.     

Suppression of food intake by intragastric glucose in rats with impaired glucose tolerance

Three experiments were performed to examine the relationship between impaired glucose tolerance and food intake. In the first experiment, normal rats that were given long-term insulin treatment, which was then withdrawn, ate less than controls when refed after food deprivation. Despite reduced intakes, rats previously treated with insulin became more hyperglycemic than controls during refeeding. In the second experiment, intragastric glucose injections reduced food intakes to a similar degree in control rats and in rats experiencing insulin withdrawal even though glucose loading produced a much greater increase in plasma glucose level in previously insulin-treated rats. In the third experiment, intragastric loads of a glucose polymer, Polycose, reduced food intake to the same degree in normal rats and in streptozotocin-diabetic rats both two and sixteen days after insulin withdrawal when diabetic rats were, respectively, hypo- and hyperphagic. The results show that impaired glucose tolerance does not appreciably alter the suppressive effects of glucose loading on food intake. Other effects of glucose administration, besides those on insulin-dependent glucose utilization, appear to reduce food intake after glucose loading.     

Effect of treadmill exercise on food intake and body weight in lean and obese rats

Body weight and food intake of lean and obese, male and female Osborne-Mendel rats following treadmill exercise were compared. Rats were assigned, separately by sex, to one of three diet groups; Group 1 was fed a low fat (10%) diet throughout the study, Group 2 was fed a high fat (55%) diet for 16 weeks and then switched to the low fat diet 1 week prior to exercise, and Group 3 was fed the high fat diet throughout the study. To control for differences in work output between the leanest and heaviest animals, exercise intensity was adjusted across groups such that all exercised rats had equivalent energy expenditure. After a 3 day training period, the exercise was successively increased over 8 days until a work output of 374.9J was reached. Relative to their respective controls, obese exercised males showed a reduction in body weight but no change in food intake. In contrast, exercised females showed no change in body weight or food intake, regardless of dietary condition.     

Effects of wheel running on food intake and weight gain of male and female rats

Adult male and female rats were housed in a sedentary condition or given free access to a running wheel for 50 days. Running wheel activity of female rats was higher than that of males throughout the experiment. Food intake, of both male and female rats that could take exercise increased, and the rate of increase of females was greater than that of males. In both males and females there was a positive correlation between food intake and running wheel activity. These findings suggest that the sex difference in the rate of increase in food intake elicited by wheel running is at least partly explained by the sex difference in running wheel activity. Although food intake increased as a function of running wheel activity, the weight gains of both sexes were slower than those of sedentary rats. In both sexes this slower weight gain was mainly due to less accumulation of fat.     

Differential effects of quinine and sucrose octa acetate on food intake in the rat

Twenty-seven adult female rats were fed chow diets containing quinine sulfate, sucrose octa acetate, or alphacel. Quinine produced a greater, more prolonged depression of food intake than did SOA. Quinine also resulted in loss of body weight.     

Sexual dimorphism in the regulation of caloric intake and body weight of rats fed different diets

Female, androgenized female (AF), and male rats were given access to 1 of 3 diets—chow (C), high-dextrose (D-chow:dextrose, 2:1), and high-fat (F-chow:Crisco, 2:1) for 2 months. Caloric intake (CI), water intake, and body weights were monitored daily. Responses to gonadectomy and a single injection of estradiol benzoate (EB) were also studied. For females, F- and C-fed rats had comparable CI's, whereas D-fed rats chronically ate much less. For males, F-fed rats overate, whereas C- and D-fed rats had comparable CI's. The pattern of CI of AF rats fed the 3 diets was intermediate between that of males and females. Male rats were less responsive to the anorexic effects of EB than were the other two groups, and the F-diet potentiated the anorexic effects of EB in all three groups. Results are discussed in terms of a sex difference in the hypothalamic regulation of feeding behavior which is modulated by gonadal hormones.     

Effect of hepatic vagotomy and/or coeliac ganglionectomy on the delayed eating response to insulin and 2DG injection in rats

The eating response that occurs following recovery from the effects of insulin or 2-deoxy-D-glucose (2DG) injection was examined in rats with hepatic vagotomy and/or coeliac ganglionectomy. Rats were deprived of food and injected with either saline (1 ml/kg), regular insulin (3 U/kg) or 2DG (200 mg/kg). Plasma glucose was measured periodically over the next 6 hr and then food was returned and intakes were measured over the next 2 hr. Rats increased food intake 6–8 hr after insulin or 2DG injection compared to the saline (control) condition. Nerve section did not affect the plasma glucose or food intake responses to insulin or 2DG injection. The results indicate that the innervation of the liver via the vagus nerve or coeliac ganglion is not involved in the delayed eating response to insulin and 2DG injection.     

Reflex insulin response associated to food intake in human subjects

The occurrence of a reflex insulin discharge at the beginning of a meal, and its possible influence on intake were studied in 7 normal weight humans. Each subject was tested twice under three standard meal conditions. The evolutions of insulinemia and glycemia were recorded over an 84 min observation period, starting 2 min before food presentation. Blood was drawn continuously from an antecubital vein, and collected in 1-min samples for the first 30 min, and then in 3-min samples. The average glycemia curve was stable until some 18-20 min after meal onset. By contrast, a significant rise in plasma insulin appeared as early as the 4th min after meal onset and it is hypothesized to be preabsorptive, of cephalic and/or gastric origin. However, inter-test variations were large even in the same person. Schematically, three types of early insulin responses were observed: high and/or sustained rise, moderate and/or short increase, moderate decrease in plasma insulin. The shape of the early insulin response was not related to any meal characteristic. The potential biological and behavioral significance of the early insulin release is discussed.     

Sex differences in the activational effects of gonadal hormones on food intake and body weight

Estrogens have been shown to decrease, and androgens to increase body weight (BWt) of guinea pigs (GPs). The magnitude of the BWt sex difference shown by intact adult GPs is due primarily to these concurrent, or activational, effects of gonadal steroids. However, a small but significant sex difference in BWt persists in animals gonadectomized at birth, indicating that early hormonal exposure may permanently influence certain steroid sensitive weight regulatory mechanisms in the two sexes. Three experiments were therefore designed to investigate the short term effects of estradiol and testosterone on food intake (FI) and BWt of gonadectomized adult male and female GPs. In the first experiment, GPs gonadectomized in adulthood were given a single injection of 6 micrograms estradiol benzoate (EB). Although EB treatment reduced FI and BWt of both females and males, significantly larger reductions occurred in females. In the second experiment, GPs gonadectomized at birth received treatments of oil or 2 micrograms EB for 7 days. EB treatment also produced significantly larger effects on FI and BWt in the neonatally gonadectomized females. The third experiment involved GPs gonadectomized as adults who were injected with either oil or 1 mg/day testosterone propionate in oil (TP) for 32 days. Compared to changes in oil injected controls, TP produced significantly larger increases in male BWt than female BWt. Therefore, although GPs show only minor sex differences in BWt which might relate to prenatal gonadal hormonal exposure, significant sex differences remain in their responsiveness to the activational effects of gonadal steroids on FI and BWt in adulthood.