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PubMed2002

Appetite sensations and eating behaviors to complete fasting in obese and non-obese individuals.

OBJECTIVE: To investigate the response of appetite sensations and eating behaviors to fasting in obese and non-obese individuals. DESIGN: Prospective study on inpatients enrolled in weight loss program including fasting at the obesity clinic, an oriental medical center in Seoul, Korea. SUBJECTS AND MEASUREMENTS: For seven obese (body mass index BMI> or =30) and 11 non-obese (BMI<30) patients, the modified visual analog scale (VAS) was administered three times per day throughout 9 days of complete fasting. Three-Factor Eating Questionnaire (TEEQ) was administered before and 18 days after the complete fasting period. RESULTS: After treatment, average weight losses were 7.4 kg (3.0 BMI) for the obese group and 6.7 kg (2.6 BMI) for the non-obese. TFEQ scales did not differ by weight status at both before and after treatments. Eighteen days after the fasting, an increase of restraint of eating was found only for the non-obese. There was a decrease of disinhibition of eating regardless of weight status. During fasting, desire to eat, hunger and prospective consumption decreased for the non-obese, while these appetite sensations tended to increase slightly for the obese. CONCLUSIONS: BMI, independent of dieting status, appeared to be related to appetite sensations except for satiety during fasting, but not before and 18 days after fasting.

Adult↗
PubMed2003

Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects.

OBJECTIVE: To study the effects of 13 weeks conjugated linoleic acid (CLA) supplementation in overweight subjects on body-weight maintenance, parameters of appetite and energy intake (EI) at breakfast after weight loss. DESIGN: This study had a double-blind, placebo-controlled randomized design. SUBJECTS: A total of 26 men and 28 women (age 37.8+/-7.7 y; body mass index 27.8+/-1.5 kg/m(2)). INTERVENTIONS: Subjects were first submitted to a very-low-calorie diet (VLCD; 2.1 MJ/day) for 3 weeks after which they started with the 13-week intervention period. They either received 1.8 g CLA or placebo per day or 3.6 g CLA or placebo per day. Additionally, subjects of the high dosage intervention replaced their habitual lunch by one meal of a protein-rich, low-energy supplement. EI was measured at breakfast and appetite profile after an overnight fast. RESULTS: The mean body weight loss was 6.9+/-1.7% of their original body weight. Multiple regression analysis showed that at the end of the 13-week intervention, CLA did not have an effect on body weight regain. Feelings of fullness and satiety were increased and feelings of hunger were decreased after 13 weeks intervention by CLA compared to placebo, independent of %body weight regain. However, EI measured at breakfast was not affected by CLA. CONCLUSION: Appetite (hunger, satiety and fullness) was favorably, dose-independently affected by a 13-week consumption of 1.8 or 3.6 g CLA/day. This did not result in a lower EI at breakfast or an improved body-weight maintenance after weight loss.

Adult↗
PubMed1999

Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men.

BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite. OBJECTIVE: The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects. DESIGN: Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol x kg(-1) min(-1)) or saline. SUBJECTS: Eight obese (body mass index, BMI, 45.5 +/- 2.3 kg/m2) male subjects. MEASUREMENTS: Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy fixed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique. RESULTS: Hunger ratings were significantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7 +/- 0.5 MJ (21 +/- 6%) by GLP-1 infusion (P = 0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6 +/- 0.35 mmol/L; nadir: 5.3 +/- 0.15 mmol/L). No nausea was recorded during GLP-1 infusion. CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this finding might be an increased satiety primarily mediated by gastric vagal afferent signals.

Adult↗
PubMed2000

Appetite after weight loss by energy restriction and a low-fat diet-exercise follow-up.

OBJECTIVE: The aim of the present study was to determine the impact of weight loss on appetite as measured by visual analog scale (VAS). METHODS: Seventeen subjects (10 men and seven women) took part in a 15 week weight loss program which consisted of drug therapy (fenfluramine 60 mg/day) or placebo coupled to an energy restriction (-2930 kJ/day; phase 1) followed by an 18 week low-fat diet-exercise follow-up (phase 2). Subjects were given a standardized breakfast before and after phase 1 as well as after phase 2. Individuals were asked to fill out VAS before and at 0, 10, 20, 30, 40, 50 and 60 min after this test meal. Blood samples were drawn before the meal and at 0, 30 and 60 min postprandially and analyzed for glucose and insulin. Fasting plasma cortisol and leptin were also determined. RESULTS: An increase in the fasting desire to eat, hunger and prospective food consumption (PFC) was observed after phase 1 and to an even greater extent after phase 2 in both men and women. In the fasting state, positive correlations were observed between changes in the desire to eat (r=0.76; P<0.05) as well as changes of PFC (r=0. 82; P<0.05) and changes in cortisol at the end of phase 1 for women. In response to phase 1, statistically significant correlations were found between changes of hunger (r=0.64; P<0.05) and desire to eat (r=0.67; P<0.05) as measured by AUC in response to the meal and changes of fasting plasma cortisol in men. The most consistent predictor of changes of baseline desire to eat (r=0.68 P<0.05), fullness (r=-0.78, P<0.05) and PFC (r=0.91, P<0.01) during phase 2 was the change in fasting cortisol in men. Changes of fullness were also associated with changes of fasting leptin in men (r=0.68; P<0. 05) during phase 2. CONCLUSION: These results suggest that weight loss is accompanied by an increase of baseline appetite in both men and women and that the most consistent predictor of these changes in appetite seems to be changes in fasting plasma cortisol.

Adult↗
PubMed2001

The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss.

OBJECTIVE: To investigate the effect of addition of modified guar gum (GG) to a low-energy semisolid meal on appetite and body weight (BW) loss. SUBJECTS: Twenty eight mainly overweight male volunteers (age, 19-56 y; body mass index, 29+/-2 kg x m(-2); BW, 89.4+/-9.2 kg). DESIGN: Baseline of one week with self-selected diet. Three treatments of 2 weeks with a low-energy diet divided over three times a day, consisting of a semisolid meal with (SSM+) or without GG (SSM) or a solid meal (SM) with the same energy content (947 kJ) and macronutrient composition, and a dinner of the subject's own choice. Washout periods lasted 4 weeks. RESULTS: Compared to baseline values, reduction in energy intake and BW loss were similar for SSM+, SSM and SM. Appetite (hunger, desire to eat or estimation of how much one could eat) was increased in SSM and in SM compared to baseline, but not in SSM+. Satiety and fullness in SSM+, SSM and SM were similar to baseline. Any intervention was more effective on BW loss when it took place the first time compared to the second and third times (2.6+/-0.2 kg, 1.7+/-0.2 kg and 1.1+/-0.2 kg, respectively; P<0.001). The SM-SSM+-SSM sequence was more effective on BW loss compared to the SSM+-SSM-SM sequence (5.6+/-1.0 and 2.5+/-0.6 kg, respectively; P<0.05). CONCLUSION: All the three treatments were equally effective with respect to BW loss. GG addition to a semisolid meal prevented an increase in appetite, hunger and desire to eat, which increase was present in the other treatments. However, differences between treatments were not statistically significant. The order effect shows that repeated 2-week bouts of dieting become increasingly ineffective. The sequence SM-SSM+-SSM was more effective than the sequence SSM+-SSM-SM, probably because compliance was relatively higher with the SSM+ or SSM diet, and compliance decreased towards the end of the complete experiment.

Adult↗
PubMed2001

The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity.

OBJECTIVE: Peripheral infusions of glucagon-like peptide-1 (GLP-1) in humans have been shown to inhibit gastrointestinal motility and decrease hunger and energy intake. However, these investigations used supraphysiological doses. The objective of this study was to investigate the effects of a GLP-1 infusion in a physiological dose on appetite sensations, energy intake, gastric emptying, energy and substrate metabolism. METHODS: Eighteen obese men participated in the placebo-controlled, randomized, single-blinded, cross-over study with infusion of GLP-1 or saline. Resting metabolic rate (RMR) and substrate oxidations were measured by ventilated hood before and after an energy-fixed breakfast. Gastric emptying was measured using paracetamol as a marker. Visual analogue scales were used to assess appetite sensations, thirst and comfort throughout the experiment and palatability of the test meals. Blood was sampled for analysis of hormones (GLP-1, GLP-2, glucose-dependent insulinotropic polypeptide (GIP), insulin, glucagon), and substrates (glucose, lactate, non-esterified fatty acids (NEFA), triacylglycerol (TAG)). Ad libitum energy intake at lunch was registered. RESULTS: Following the breakfast, GLP-1 infusion suppressed ratings of hunger and prospective food consumption (P<0.05), whereas all other subjective ratings and ad libitum energy intake were unaffected. RMR, carbohydrate oxidation and gastric emptying rate were lower during the GLP-1 infusion compared with the saline infusion (P<0.001, P<0.05, P<0.0001, respectively). All plasma hormone and substrate profiles, except NEFA, were significantly reduced by GLP-1 (P<0.0001). CONCLUSION: It is concluded that GLP-1 in physiological concentrations powerfully reduces the rate of entry of nutrients into the circulation by a reduction of gastric emptying rate in obese subjects. The effect of GLP-1 on appetite and food intake may be beneficial in weight reduction.

Adult↗
PubMed2002

Comparison of oral and gastric administration of sucrose and maltose on gastric emptying rate and appetite.

OBJECTIVES: To investigate mechanisms by which specific sugars affect feeding behaviour. DESIGN: In an initial study, gastric emptying rate and appetite were measured following ingestion of lemon flavoured solutions of sucrose, maltose (2160 kJ, 575 ml) and water control (67 kJ, 575 ml) given in randomised order on separate days to six male volunteers. In a second study, the effects of intragastric infusions of sucrose and maltose on appetite and gastric emptying were compared in six male volunteers. RESULTS: When given orally, both the sucrose and maltose solutions slowed gastric emptying compared with water, however sucrose emptied at a faster rate than maltose. The sucrose preload increased fullness and decreased prospective consumption during the following 3 h compared with maltose and water. When administered intragastrically, the gastric emptying rate of sucrose was again faster than that of maltose but there was no difference in ratings of hunger, fullness or prospective consumption for 3 h following the infusions. CONCLUSIONS: These results show that gastric emptying of sucrose is faster than that of maltose and suggest that gastric emptying rate and hence period of gastric distension is not the predominant factor regulating appetite by these sugars. The differences observed between oral and gastric delivery suggest that oro-sensory and cognitive factors, possibly stimulated by the sweetness of sucrose, were involved in the induction of satiety.

Administration, Oral↗
PubMed2003

Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal.

OBJECTIVE: To examine the short-term effects of a lipase inhibitor (Orlistat) on physiological and behavioural measures of appetite in response to a high-fat meal. DESIGN: Randomised, single blind, placebo-controlled, crossover trial. SUBJECTS: A total of 19 healthy nonobese male subjects. PROCEDURES: After an overnight fast, subjects ingested a test meal of 2940 kJ (60% fat, 30% CHO, 10% protein) with Orlistat (120 mg) or a placebo, separated by 2 weeks. Appetite, as assessed by a standard line scale, and plasma cholecystokinin (CCK) concentrations were measured prior to and every hour after the test meal for 4 h. Thereafter, subjects ingested a quantified, but self-selected portion of a standardised lunch (15% protein, 37% fat and 45% CHO), before completing a final line scale questionnaire. RESULTS: The CCK response to the test meal was negatively correlated with BMI in both the Orlistat and placebo trials (R=-0.69 and -0.65, P<0.01). Orlistat administration did not significantly alter the CCK response to the test meal (6.30+/-3.27 vs 7.36+/-3.94 pM min, for Orlistat and placebo, P=0.193). Similarly, the line scale measures of appetite and subsequent intake (520+/-205 vs 554+/-197 g, P=0.48) were not different between the trials. CONCLUSION: Orlistat administration did not alter short-term physiological or behavioural measures of satiety in response to a high-fat meal in healthy, nonobese subjects. The CCK response to a test meal may be partly determined by BMI.

Adult↗
PubMed2004

Effects of manipulated palatability on appetite depend on restraint and disinhibition scores from the Three-Factor Eating Questionnaire.

OBJECTIVES: The present study evaluated the effects of dietary restraint on short-term appetite in response to manipulated palatability. DESIGN: The effects of palatability on appetite during a lunchtime meal were assessed by contrasting intake of a bland and palatable version of a simple food (within subject). To test how responses to palatability varied with restraint, these meals consumed by women were classified according to restraint (R) and disinhibition (D) scores from the Three-Factor Eating Questionnaire (TFEQ) as high R/high D (HR-HD), high R/low D (HR-LD), low R/high D (LR-HD) and low R/low D (LR-LD). SUBJECTS: A total of 40 normal-weight women subdivided into four groups based on TFEQ scores. MEASUREMENTS: The overall intake, appetite and hedonic ratings before, during and after the meal. RESULTS: All groups ate similar amounts of the bland food, but the LR-HD group ate significantly more of the palatable version than the other groups, whereas HR-LD did not increase intake in response to palatability. Hunger increased on tasting the palatable food in all but the HR-LD group, and this group ended both meals more hungry/less full than the others. CONCLUSION: Women classified as HR-LD were unresponsive to manipulated palatability, whereas those classified as LR-HD were over-responsive. These findings imply that some individuals are prone to over-respond to palatability and so are at greater risk of developing obesity, whereas others are able to resist the effects of palatability and so successfully self-restrict their food intake. Implications for obesity are discussed.

Adult↗
PubMed2005

Inhibition of appetite by nasal leptin administration in rats.

OBJECTIVE: Leptin inhibits appetite and reduces body weight. However, subcutaneous leptin administration is not very effective on weight reduction. The present studies were undertaken to test the hypotheses that nasally administered leptin effectively accesses to the brain and inhibits appetite. METHODS: Recombinant leptin (0.5 mg/rat) was administered into the bilateral nasal spaces of rats (i.n.). Changes in serum immunoreactive leptin (IRL) and cerebrospinal fluid (CSF)-IRL concentrations after i.n. leptin administration were compared after intraperitoneal (i.p.) administration. The influence of 0.1 or 0.5% lysophosphatidylcholine (LPC) as an optimizer of leptin absorption was examined. The anorexic effects of i.n. leptin were compared with i.p. leptin in ad libitum fed rats. RESULTS: The i.n. leptin increased CSF-IRL concentrations, although serum IRL concentrations of rats administered leptin i.n. were lower than those administered i.p. The addition of 0.1 and 0.5% LPC dose-dependently increased serum IRL concentrations, but did not modify CSF-IRL concentrations in i.n. leptin-treated rats. The i.n. leptin inhibited dark-time food consumption at 0-1 h and 3-6 h in ad libitum fed rats. In contrast, i.p. leptin reduced food consumption only for an hour. Phosphorylated signal transducer and activator of transcription (STAT) 3 immunoreactive cells increased in the arcuate nucleus (ARC) of the hypothalamus at 3 h only following i.n. leptin. CONCLUSION: The present study demonstrated that i.n. leptin caused longer inhibition of appetite and phosphorylation of STAT3 in ARC. It is concluded that the trans-nasal route may be useful for the selective access of leptin to the brain in obese people.

Administration, Inhalation↗
PubMed2000

Seasonal changes in the expression of neuropeptide Y and pro-opiomelanocortin mRNA in the arcuate nucleus of the ovariectomized ewe: relationship to the seasonal appetite and breeding cycles.

Sheep experience well-documented seasonal changes in reproductive activity and voluntary food intake (VFI). Within the hypothalamus, neurones that express neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) have been implicated in the regulation of reproduction and appetite. In this study, we aimed to determine the extent to which the expression of these two neuronal systems is linked to the seasonal reproductive cycle and/or the seasonal appetite cycle. VFI in our sheep reaches a nadir in August with no difference occurring between December and February. We examined the brains of ovariectomized (OVX) female sheep (n=5-7) that were killed during the breeding season (February) or during the early or late nonbreeding season (August and December, respectively). The brains of these animals were perfused with paraformaldehyde and processed for in situ hybridization histochemistry, using ribonucleotide probes labelled with 35S. The number of NPY and POMC cells and the number of silver grains per cell were counted using an image analysis system. For NPY, the number of cells counted in the arcuate nucleus/median eminence region and the number of silver grains per cell was significantly lower in animals killed during August than in animals killed in February or December. The number of grains per cell over NPY cells was also significantly lower in animals killed during August. For POMC, the number of cells was lower in February than in August and December. Similarly, the number of grains per cell for POMC were lower in February than in August and December. VFI was significantly lower in animals during August than at other times of the year. We conclude that in OVX ewes: (i) NPY gene expression is lower at the time of the year when VFI is reduced and (ii) POMC gene expression is greater at the time of the nonbreeding season than during the breeding season. Because these results were obtained in OVX animals, the changes appear to be independent of alterations in the secretion and/or action of ovarian steroids. Thus, the activity of NPY neurones appears to relate to changes in appetite whereas changes in POMC expression may be relevant to the seasonal breeding cycle.

Animals↗
PubMed2003

Links between the appetite regulating systems and the neuroendocrine hypothalamus: lessons from the sheep.

The hypothalamus is integral to the regulation of energy homeostasis and the secretion of hormones from the pituitary gland. Consequently, hypothalamic systems may have a dual purpose in regulating both neuroendocrine function and appetite. To date, most studies investigating the interface between appetite and hormone secretion have been performed in rats or mice that have been acutely fasted or baring a genetic abnormality causing either obesity or aphagia. By contrast, various physiological models, including chronic food-restriction or photoperiodically driven changes in voluntary food intake, add further perspective to the issue. In this regard, sheep provide an innovative model whereby long-term changes in body weight or extended feeding rhythms can be investigated. This review compares and contrasts data obtained in different species with regard to the neuroendocrinology of appetite, and discusses the benefits and knowledge gained from using various nonrodent models with a particular emphasis on a ruminant species.

Animals↗
PubMed2002

The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics.

BACKGROUND: Previous studies reported that administration of first generation alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake. OBJECTIVES: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured. DESIGN: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption. RESULTS: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test. CONCLUSIONS: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.

1-Deoxynojirimycin↗
PubMed2001

The effect of acute hyperglycaemia on appetite and food intake in Type 1 diabetes mellitus.

AIMS: To determine the effects of acute hyperglycaemia on appetite and food intake in Type 1 diabetes mellitus. METHODS: Two separate studies, each involving eight adults with uncomplicated Type 1 diabetes, were performed: one in the fasted state (A) and the other after a nutrient preload (B). In both studies, perceptions of appetite (hunger and fullness) and food intake at a buffet meal were evaluated during euglycaemia (blood glucose, approximately 6 mmol/l) and hyperglycaemia (blood glucose, approximately 14 mmol/l). Both experiments were randomized and single-blind. In study A, appetite was assessed in the fasted state for 90 min before the buffet meal. In study B, a nutrient 'preload' of Ensure and milk containing 13C-octanoic acid was consumed 90 min before the meal. Gastric emptying of the preload was quantified with a radioisotopic breath test technique. RESULTS: There was no significant difference in plasma insulin concentrations between euglycaemia and hyperglycaemia in either study. In study A, there were no differences in hunger, fullness or energy intake between the two treatment days. In study B, subjects were slightly less hungry between the preload and buffet meal during hyperglycaemia than euglycaemia (P = 0.04), and tended to have slower gastric emptying during hyperglycaemia (emptying coefficient, 3.89 +/- 0.16 vs. 3.57 +/- 0.21; P = 0.052), but there was no difference in food intake between hyperglycaemia and euglycaemia. CONCLUSIONS: Acute hyperglycaemia suppresses hunger after a nutrient preload, but not in the fasted state, in patients with uncomplicated Type 1 diabetes. This effect is small and not associated with changes in food intake.

Adolescent↗
PubMed1998

The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs.

BACKGROUND: After case reports of cardiac-valve abnormalities related to the use of appetite suppressants were published, we undertook a study to determine the prevalence of the problem using transthoracic echocardiography. METHODS: We examined patients who had taken dexfenfluramine alone, dexfenfluramine and phentermine, or fenfluramine and phentermine for various periods. We enrolled obese patients who had taken or were taking these agents during open-label trials from January 1994 through August 1997. We also recruited subjects who had not taken appetite suppressants and who were matched to the patients for sex, height, and pretreatment age and body-mass index. The presence of cardiac-valve abnormalities, defined by the Food and Drug Administration and Centers for Disease Control and Prevention as at least mild aortic-valve or moderate mitral-valve insufficiency, was determined independently by at least two cardiologists. Multivariate logistic-regression analysis was used to identify factors associated with cardiac-valve abnormalities. RESULTS: Echocardiograms were available for 257 patients and 239 control subjects. The association between the use of any appetite suppressant and cardiac-valve abnormalities was analyzed in a final matched group of 233 pairs of patients and controls. A total of 1.3 percent of the controls (3 of 233) and 22.7 percent of the patients (53 of 233) met the case definition for cardiac-valve abnormalities (odds ratio, 22.6; 95 percent confidence interval, 7.1 to 114.2; P<0.001). The odds ratio for such cardiac-valve abnormalities was 12.7 (95 percent confidence interval, 2.9 to 56.4) with the use of dexfenfluramine alone, 24.5 (5.9 to 102.2) with the use of dexfenfluramine and phentermine, and 26.3 (7.9 to 87.1) with the use of fenfluramine and phentermine. CONCLUSIONS: Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or dexfenfluramine and phentermine had a significantly higher prevalence of cardiac valvular insufficiency than a matched group of control subjects.

Adult↗
PubMed2004

Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor.

Synthetic agonists of the growth hormone secretagogue receptor (GHSR) rejuvenate the pulsatile pattern of GH-release in the elderly, and increase lean but not fat mass in obese subjects. Screening of tissue extracts in a cell line engineered to overexpress the GHSR led to the identification of a natural agonist called ghrelin. Paradoxically, this hormone was linked to obesity. However, it had not been directly shown that the GHSR is a physiologically relevant ghrelin receptor. Furthermore, ghrelin's structure is significantly different from the synthetic agonist (MK-0677) used to expression-clone the GHSR. To address whether the GHSR mediates ghrelin's stimulatory effects on GH release and appetite, we generated Ghsr-null mice. In contrast to wild-type mice, acute treatment of Ghsr-null mice with ghrelin stimulated neither GH release nor food intake, showing that the GHSR is a biologically relevant ghrelin receptor. Nevertheless, Ghsr-null mice are not dwarfs; their appetite and body composition are comparable to that of wild-type littermates. Furthermore, in contrast to suggestions that ghrelin regulates leptin and insulin secretion, fasting-induced changes in serum levels of leptin and insulin are identical in wild-type and null mice. Serum insulin-like growth factor 1 levels and body weights of mature Ghsr-null mice are modestly reduced compared to wild-type littermates, which is consistent with ghrelin's property as an amplifier of GH pulsatility and its speculated role in establishing an insulin-like growth factor 1 set-point for maintaining anabolic metabolism. Our results suggest that chronic treatment with ghrelin antagonists will have little effect on growth or appetite.

Animals↗
PubMed2000

The inhibitory effect of hormones associated with stress on Na appetite of sheep.

Stress is a large stimulus of Na appetite in rabbits, rats, and mice. This study investigated the influence of some peptides implicated in stress, i.e., adrenocorticotropin (ACTH), corticotropin-releasing factor (CRF), and the recently discovered member of the CRF family, urocortin, on the ingestive behavior of sheep. Intracerebroventricular infusion of these peptides over 4 days decreased the need-free Na intake of Na-repleted sheep. Intracerebroventricular infusion of urocortin, however, did not alter Na intake of Na-depleted sheep. Systemic infusion of ACTH increased, whereas systemic infusion of either urocortin or CRF decreased, Na intake of Na-repleted sheep. The increase in Na intake caused by the peripheral infusion of ACTH was blocked by concurrent i.v. infusion of urocortin, substantiating the inhibitory role of this peptide on Na appetite. Central administration of all peptides and i.v. administration of urocortin or urocortin and ACTH combined decreased food intake. Water intake was not directly influenced by the peptides. Rather, decreased water intake, when observed, was secondary to decreased food intake, as determined by pair-feeding experiments. Whereas systemic infusion of ACTH mimics the increase in Na intake observed in several different stressful situations, CRF and urocortin actually inhibit Na intake, indicating a direct central action overriding any effect of these peptides on ACTH release. Indeed, the inhibition of Na intake by urocortin occurred despite its stimulation of ACTH release and the subsequent increase in peripheral level of cortisol. Thus it would appear that hormones associated with stress have both excitatory and inhibitory influences on Na intake. Presumably, other physiological processes entrained by stress also will be important in determining the quantitative outcome on Na appetite.

Adrenocorticotropic Hormone↗
PubMed2005

Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens.

Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. In addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as d-amphetamine, were determined on Pavlovian autoshaping in rats, which assesses learning by discriminated approach behavior to a visual conditioned stimulus predictive of food reward. Intracerebral infusions were given either immediately after each conditioning session to disrupt early memory consolidation or after a delay of 24 h. Findings indicate that immediate, but not delayed, infusions of both D1 (SCH 23390) and NMDA (AP-5) receptor antagonists significantly impair learning on this task. By contrast, amphetamine and the D2 receptor antagonist sulpiride were without significant effect. These findings provide the most direct demonstration to date that D1 and NMDA receptors in the NAc contribute to, and are necessary for, the early consolidation of appetitive Pavlovian learning.

Animals↗