In vitro effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge.

OBJECTIVE: The purpose of this work was to study the direct effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge. METHODS: LH responsiveness to leptin by pituitaries from rats killed in the afternoon (1500 h) at different stages of the 4-day estrous cycle (diestrus-1: D1; diestrus-2: D2; proestrus; estrus), ovariectomized (OVX; 15 days post-castration) and ovariectomized steroid-primed (OVX-E(2)/Pg; pretreated with 5 microg estradiol and 1 mg progesterone), was evaluated in vitro. Hemi-adenohypophyses were incubated in the presence of synthetic murine leptin for 3 h. RESULTS: Addition of increasing concentrations of leptin (0.1-100 nmol/l) to the incubation medium of proestrus pituitaries produced a dose-related stimulation of LH release; the maximal increase to 315% of control was obtained with 10 nmol/l leptin. Leptin (10 nmol/l) enhanced LH release at all days of the estrous cycle, the greatest response occurring in proestrus (318%) and the lowest at D1 (123%). In order to evaluate the role of nitric oxide (NO) in the action of leptin on LH release, glands from proestrus rats were incubated in the presence of 10 nmol/l leptin with or without 0.3 mmol/l N(G)-monomethyl-l-arginine (NMMA), a competitive inhibitor of NO synthase (NOS). NMMA completely suppressed the stimulation of LH release induced by leptin. Leptin also stimulated LH release by pituitaries from OVX rats, and treatment with steroid hormones led to a marked increase in the response (OVX: 162% compared with OVX-E(2)/Pg: 263%; P<0.05). For comparative analysis, a similar experimental procedure was carried out using GnRH (10 nmol/l). Leptin acts at the pituitary level in a similar manner as GnRH, although with significantly lower potency. CONCLUSIONS: These results confirm and extend previous reports regarding a direct action of leptin at the pituitary level, stimulating LH release by anterior pituitaries from female rats at the time of spontaneous and steroid-induced LH surge. In the female rat pituitary this leptin action is controlled by gonadal steroids and mediated by NO.

Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine.

BACKGROUND: Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits. PATIENTS AND METHODS: Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo. RESULTS: In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01). CONCLUSION: Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year.

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE: The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA: The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS: The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS: The cost per quality-adjusted life year saved was $10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS: Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.

Role of vasoactive intestinal peptide and 5-HT2 receptor subtype in serotonin stimulation of basal and thyrotropin-releasing-hormone-induced prolactin release in vitro from rat pituitary cells.

We have previously demonstrated that 5-HT stimulates not only basal but also thyrotropin-releasing-hormone (TRH)-induced prolactin (PRL) release by acting directly at the pituitary gland level. In the present report, the participation of an autoparacrine action of VIP in the stimulatory effects of 5-HT and the involvement of the 5-HT2 receptor type in mediating serotonin-induced PRL release have been examined. Cultured anterior pituitary cells from ovariectomized adult rats were incubated for 1 h in 1 ml of T3-supplemented medium with or without the test substances. The results obtained in the presence of T3 confirm our previous observations, since treatment of the cells with 5-HT caused dose-dependent increases in basal PRL release, with an approximate EC50 of 3.68 x 10(-8) M, and led to a significant potentiation (1.3-fold) of the TRH-induced PRL release. In order to evaluate the possible participation of vasoactive intestinal peptide (VIP) as mediator of the effects of 5-HT on PRL release, cells were incubated in the presence of 5-HT alone (3-1,000 nM) or 100 nM 5-HT plus 30 nM TRH, with or without 200 nM VIP antagonist (VIP-At): [D,4-Cl-Ph6,Leu17]VIP. VIP-At partially inhibited the release of PRL induced by 5-HT, both basal and TRH-stimulated release. The stimulatory effect of 5-HT, however, was not eliminated by VIP-At, since the PRL released in response to 5-HT was still over the respective control ones. These results further support the findings suggesting that 5-HT acts directly at pituitary level by stimulating PRL release. Addition of the 5-HT2 receptor antagonist, ketanserin (1 microM) into the incubation medium resulted in the loss of cellular responsiveness to 5-HT, preventing not only the stimulatory effect of 5-HT on the basal but also on the TRH-induced PRL release. In conclusion, the results further strengthen the possibility that 5-HT increases the basal PRL release and potentiates the stimulatory effect of TRH by acting directly at the level of the lactotropes. These effects are not simply a consequence of autoparacrine action of VIP. In addition, it was shown that ketanserin completely antagonizes PRL response to 5-HT, indicating the involvement of the 5-HT2 receptor type in mediating PRL release.

Effect of cycloheximide and tunicamycin on the gonadotrophin-releasing hormone stimulated distal glycosylation of luteinizing hormone by rat pituitary cells.

We have previously demonstrated that gonadotrophin-releasing hormone (GnRH) induces not only changes in quantity but also in quality on secreted luteinizing hormone (LH), by increasing [14C]Leu (translation) and [3H]Gal (distal glycosylation) incorporation into newly synthesized hormone. In the present report, we have further examined the GnRH-induced [3H]Gal-LH synthesis and release by treating anterior pituitary cells with polypeptide synthesis and glycosylation inhibitors (cycloheximide and tunicamycin, respectively). Pituitary cells from ovariectomized adult rats were cultured for 4 days and then incubated for different periods (0-5 h) in medium containing [14C]Leu plus [3H]Man or [14C]Leu plus [3H]Gal in the absence (basal) or presence of 10 nmol/L GnRH with or without (control) cycloheximide (1.0 and 4.0 microg/mL) or tunicamycin (0.5 and 2.0 microg/mL). At the end of each incubation period, the cells and the medium were separated and processed for DNA uptake and newly synthesized LH (labeled LH, by immunoprecipitation with a-betaLH) determinations. The velocity of synthesis and release (between 0 and 2 h, and between 2 and 5 h) was calculated by regression analysis and the statistical significance of differences was determined by the slope test. GnRH enhanced the rates of synthesis and release of [14C]Leu-, [3H]Man-, and [3H]Gal-LH to 157 and 237; 164 and 190; and 272 and 508% of basal values, respectively. Cycloheximide totally blocked synthesis and release of [14C]Leu-LH and greatly reduced those of [3H]Man-LH, resulting in the loss of cellular responsiveness to GnRH. Addition of tunicamycin to the pituitary cells inhibited the rates of synthesis and release of [3H]Man-LH which had been induced by GnRH, without altering those of [14C]Leu-LH. These findings indicate that glycosylation is not a condition for GnRH-stimulated LH translation. The GnRH-increased [3H]Gal-LH rates of synthesis and release were affected to a lesser extent by the inhibitors. Thus, GnRH stimulation of distal glycosylation can occur, albeit at a reduced rate, even though protein synthesis and glycosylation are blocked. In conclusion, the present results corroborate that GnRH stimulates the addition of galactose residues into LH molecule. This effect is not simply the consequence of stimulating LH polypeptide chain synthesis. In addition, it is shown that GnRH-increased LH translation is independent of glycosylation.

Plasma levels of tissue plasminogen activator and plasminogen activator inhibitor-1 are correlated with the presence of transplant coronary artery disease in cardiac transplant recipients.

Hemostatic factors are involved in the pathogenesis of native coronary artery disease. However, their role in transplant coronary artery disease is less established. To assess the role of hemostatic factors in transplant coronary artery disease we studied 52 consecutive cardiac transplant patients. The presence of transplant coronary artery disease was determined by angiography. Plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand Factor (vWF), and fibrin D-dimer were determined by enzyme-linked immunosorbent assays. Serum lipids were measured by enzymatic methods. Patients with transplant coronary artery disease had higher circulating t-PA (8.6 +/- 0.8 vs. 5.4 +/- 0.6 ng/ml, p = 0.021) and PAI-1 antigen concentrations (38.0 +/- 3.4 vs 25.8 +/- 2.2 ng/ml, p = 0.037). t-PA and PAI-1 antigen concentrations correlated with the severity of angiographic disease (R = 0.34; p = 0.014 for t-PA, and R = 0.45; p = 0.001 for PAI-1). Serum cholesterol levels were higher in patients with transplant coronary artery disease (221 +/- 7.6 vs 191 +/- 9.2 mg/dl, p = 0.039). Serum triglycerides were also higher in patients with transplant coronary artery disease by angiography (246 +/- 38.3 vs 139 +/- 20.8 mg/dl, p = 0.050). Multivariate analysis identified t-PA antigen (p = 0.003) and triglyceride levels (p = 0.038) as independent predictors for the presence of transplant coronary artery disease. We conclude that cardiac transplant patients with evidence of transplant coronary artery disease on coronary angiography have altered hemostatic function which is reflected by elevated levels of circulating t-PA and PAI-1 antigens. The interaction of the hemostatic system and serum lipids in the development of transplant coronary artery disease warrants further study.

Increase in diet-induced thermogenesis at the start of refeeding in severely malnourished anorexia nervosa patients.

Many reports describe the difficulty for anorexia nervosa patients to gain weight during refeeding. To assess whether an increase in diet-induced thermogenesis (DIT) participates to this resistance, we studied DIT by indirect calorimetry in 11 severely malnourished anorexia nervosa patients [body mass index (BMI; in kg/m2) = 13] to accomplish two purposes: 1) to compare DIT in a strict semistarvation state with that obtained after 1 wk refeeding, when metabolism is shifted to a dynamic trend toward regaining weight, without significant change in body composition; 2) to study the effect on DIT of two energetic loads representing each one-third of the energy intake during semistarvation and refeeding, respectively: 1.25 and 2.92 MJ. To avoid bias, the two liquid loads were infused intragastrically in a random double-blind fashion. A significant increase in DIT during refeeding was observed for the two loads (204 +/- 23 kJ for the 1.25-MJ liquid meal and 482 +/- 78 kJ for the 2.92-MJ one, P < 0.02). The higher the load, the larger the increase with refeeding (P < 0.001). This increment in DIT exceeded the increase in active lean body mass and was poorly correlated with lean body mass. These results provide clear evidence of a strong cellular "waste" mechanism in anorexia nervosa patients during the early phase of refeeding, which enhances the adaptative resistance to overfeeding that we have already shown for resting energy expenditure.

Rates of proximal and distal glycosylation of luteinizing hormone by cultured rat pituitary cells.

The purpose of the present work was to study the rate of basal luteinizing hormone (LH) glycosylation, discriminating the co-translational (proximal) and the post-translational (distal) glycosylation. The experiments were performed to determine the temporal relationship between the biosynthesis of the peptide chains (by [14C]leucine incorporation: [14C]Leu-LH) and the proximal (by [3H]mannose incorporation: [3H]Man-LH) and distal (by [3H]galactose incorporation: [3H]Gal-LH) glycosylation of LH, by rat pituitary cells in primary culture. In addition, the effects of cycloheximide (translation inhibitor) and tunicamycin (glycosylation inhibitor) on the rates of synthesis and release of [3H]Man-LH and [3H]Gal-LH were studied. The rates of synthesis and release (between 0 and 2 h and between 2 and 5 h) were calculated by regression analysis and the statistical significance of differences was determined by the slope test. The rate of synthesis of [3H]Man-LH (slope = 45.59) parallelled that of [14C]Leu-LH (slope = 41.39), which was in agreement with the assumption that the addition of the high mannose core is a co-translational event. Release of [3H]Man-LH (slope = 4.32) as well as that of [14C]Leu-LH (slope = 2.53) showed a lag period of approximately 2 h. The dynamics of [3H]Gal-LH secretion over the course of incubation, with a slower rate of synthesis (slope = 26.40) and a faster rate of release (slope = 6.34), differed from that of [3H]Man-LH. LH labeled with [3H]Gal was released from the early times of the incubation, indicating that galactose is added in the final stages of the secretory process into LH molecules, which are immediately released. LH translation blockage induced by cycloheximide was associated with a corresponding decrease of [3H]Man incorporation. On the other hand, addition of tunicamycin to the pituitary cells inhibited the rates of synthesis and release of [3H]Man-LH, without affecting those of [14C]Leu-LH. These findings show that proximal glycosylation depends on synthesis of the peptide chains, whereas the addition of the polymannose core is not a condition for translation. The rates of synthesis and release of [3H]Gal-LH were less affected by the antibiotics, and the inhibition was only significant at higher doses and long-time treatments. The present results demonstrate the independence of both steps of LH glycosylation, the rate of [3H]Gal-LH synthesis being 1.7-fold slower and that of release 1.5-fold faster than those of [3H]Man-LH, respectively. The data also suggest that glycosylation is not an essential step in the LH secretory process since the hormone, which is normally secreted in a glycosylated form, was synthesized, transported, and released without the carbohydrate side chains.

Hind III polymorphism of the lipoprotein lipase gene and plasma lipid response to low calorie diet.

OBJECTIVE: To assess the effects of a low calorie diet on plasma lipids according to the Hind III polymorphism of the lipoprotein lipase (LPL) gene in overweight patients. DESIGN: Diet intervention study (25% restriction in energy intake during 2.5 months) in relation to genetic factors. SUBJECTS: 115 unrelated patients (77 women and 38 men) recruited on the basis of 120% of ideal body weight. MEASUREMENTS: Body weight, body mass index, blood lipids and lipoproteins, at entry and after 2.5 months, determination of LPL Hind III genotypes. RESULTS: On spontaneous diet, lipid and lipoproteins differed significantly between Hind III genotypes. Homozygous subjects for the presence of the Hind III cutting site, H2H2, had significantly higher plasma and VLDL triglyceride and apolipoprotein B concentrations than subjects carrying H1 allele. H2H2 subjects reduced their VLDL-triglyceride and apolipoprotein B concentrations more than H1 carriers, in such a way that differences in lipid levels according to genotypes were no more significant after diet. The magnitude of the decrease in triglycerides was positively correlated with the initial concentration but, among hypertriglyceridemic subjects, H2H2 still had the largest decrease in plasma and VLDL-triglycerides. CONCLUSION: The genetic variation at the LPL gene locus affects the response of serum lipid levels to caloric restriction. Overweight subjects with the H2H2 genotype of the LPL Hind III polymorphism are predisposed to hypertriglyceridemia but they are good responders to diet in terms of lipid levels.

A short-term cognitive behavioural therapy for bulimia nervosa including brief hospitalisation.

This was a metabolic study of bulimia nervosa required to design short-term cognitive-behavioural therapy (CBT) beginning with a brief admission to a psychiatric ward. The treatment produced significant improvements in eating behaviour and results are compared with those of previously published studies. The comparisons do not suggest that brief admission at the onset of therapy might enhance its effectiveness. In other respects, increase in normal meal intake was found to correlate significantly with decrease in hinging. This supports the notion that appropriate food intake at meal times should be an important issue in CBT for bulimia nervosa.

GnRH-stimulated glycosylation (proximal and distal) of luteinizing hormone by cultured rat pituitary cells.

In the present work, the effects of GnRH on the translation (by [14C]leucine incorporation; [14C]Leu-LH) and the glycosylation of LH by rat pituitary cells in primary culture were established. The use of specific markers as radioactive precursors made it possible to discriminate the action of the neurohormone on proximal glycosylation (by[3H]mannose incorporation; [3H]Man-LH) as well as distal glycosylation (by [3H]galactose incorporation; [3H]Gal-LH) in the course of synthesis and release of LH. Pituitary cells from ovariectomized adult rats were incubated for different periods between 0 and 5 h in medium containing [14C]Leu plus [3H]Man or [14C]Leu plus [3H]Gal with or without 10 nM GnRH. GnRH increased synthesis and release of newly synthesized LH. The magnitude of the stimulatory effect on the kinetics of [14C]Leu (slope = 63.58; 158% of control) and [3H]Man (slope = 75.15; 161%) incorporation to LH was similar. The action of the neurohormone appears to be exerted on translation, the increased [3H]Man incorporation being a secondary phenomenon arising from the greater amount of available polypeptide chains as acceptors of the polymannose core. However, a direct effect of GnRH on proximal glycosylation cannot be excluded. GnRH also stimulated the kinetics of release of [14C]Leu-LH (slope = 6.14; 236% of control) and [3H]Man-LH (slope = 8.06; 191%). Comparatively, the effect of GnRH on [3H]Gal-LH was detected earlier than that on LH labeled with the other precursors; increases in rates of production (slope = 71.57; 278% of control) and release (slope = 32.08; 494%) were higher than those in [14C]Leu- and [3H]Man-LH kinetics, indicating that GnRH acts specifically on this distal step of LH glycosylation. GnRH enhanced the relative terminal glycosylation ([3H]Gal/[14C]Leu ratio) of total and release LH without modifying the relative proximal glycosylation ([3H]Man/[14C]Leu ration) of the hormone. We conclude that GnRH can induce not only changes in the quantity (greater number of molecules) but also in the quality (molecules more glycosylated) of the secreted LH by acting directly at translation and distal glycosylation level.

Polymorphisms of uncoupling protein (UCP) and beta 3 adrenoreceptor genes in obese people submitted to a low calorie diet.

OBJECTIVE: To investigate whether the genetic polymorphisms of the uncoupling protein (UCP) and beta 3 adrenergic receptor (beta 3 AR) were associated with differences of weight loss in obese patients submitted to a low calorie diet. DESIGN: Longitudinal, clinical intervention study of a 25% restriction in energy intake with respect to genotypes. SUBJECTS: 163 patients with a body mass index above 27. MEASUREMENTS: Body weight and body mass index at baseline and after 2.5 months, genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: For the UCP polymorphism, two alleles, 1 and 2 were identified with respective frequencies of 0.27 and 0.73. The allele 1 was associated with lower body weight loss after diet: 4,6,5.7 and 7.1 kg for the 1-1, 1-2 and 2-2 genotypes respectively (P < 0.05). No difference in weight loss was found according to the beta 3 AR Trp64Arg mutation. CONCLUSIONS: A genetic variant of the UCP gene is associated with a resistance to low calorie diet. This result, together with previous data on body weight gain, supports the hypothesis of a role of UCP and brown adipose tissue in the body weight regulation in humans. The importance of the Trp64Arg mutation of the beta 3 AR in the resistance to low calorie diet is still to demonstrate.

High resting energy expenditure in normal-weight bulimics and its normalization with control of eating behaviour.

Resting energy expenditure (REE) has been found to be lower in normal weight-bulimics (NWBs) than in controls and it was speculated that metabolic abnormalities might underlie bulimia. This study consisted of a longitudinal assessment of REE, body composition and energy intake before, during and after the control of eating behaviour, with comparisons between REEs in NWBs, those in controls, and estimated basal energy expenditure (EBEE). NWBs in acute phase of bulimia were assessed the 1st, 2nd, and last day of a one-week hospitalization that warranted compliance with normal diet. Assessments were then repeated after a six-week outpatient psychotherapy. Mean REE in NWBs was higher than that in controls and EBEE on admission. It decreased down to normal rate at discharge and at therapy termination. Fat-free mass (FFM) decreases slightly during hospitalization despite a weight-maintenance diet, but REE-FFM ratio also decreased significantly. Metabolic factors which might account for these results are discussed. Data suggest that: (1) caloric requirements in NWBs were higher than estimated weight-maintenance rations; (2) binge-eating increased REE; (3) control of eating behaviour decreased REE.

Histologic appearance of transmyocardial laser channels after 4 1/2 weeks.

Preliminary results of clinical studies suggest that transmyocardial laser revascularization is an effective treatment for patients with chronic angina that cannot be treated by other means. The mechanism of this effect remains controversial. We present autopsy results from a patient obtained 4 1/2 weeks after operation that show that the channels do not maintain patency. Further work is needed to determine the frequency of channel patency and its relation to clinical benefit.

Kinetics of translation and glycosylation of pituitary glycoproteins.

The present study determines the basal kinetics of synthesis of translation (by [14C] leucine incorporation, [14C]leu-PROT] and of proximal (by [3H]mannose incorporation, [3H]man-PROT) and distal (by [3H]galactose incorporation, [3H]gal-PROT) glycosylation of total adenohypophyseal glycoproteins, by rat pituitary cells in primary culture. In order to obtain more information regarding the role of both steps of glycosylation on the secretory process, the effects of cycloheximide (CH; translation inhibitor) and tunicamycin (TM;glycosylation inhibitor) on the kinetics of synthesis and release of pituitary glycoproteins were also studied. Cells were incubated in medium containing [14C]leu plus [3H]man or [14C]leu plus [3H]gal, for various time-intervals (from 0.5 to 5 h) in the absence (control) or presence of different doses of CH (1.0; 4.0 or 16.0 micrograms/ml) or TM (0.5; 1.0 or 2.0 micrograms/ml). The kinetics of synthesis (slope = 3488) and release (slope = 622) of [14C]le-PROT were higher than those of the sugar precursors (slopes: [3H]man-PROT = 1751 and 526; [3H]gal-PROT = 1231 and 506). Leucine or mannose-labeled protein was barely detectable in the medium after 2 h incubation, whereas galactose-labeled protein had already been released into the incubation medium by 30 min. Cycloheximide induced translation blockage and, concomitantly, produced a marked inhibition of [3H]man incorporation. On the other hand, TM inhibited the kinetics of synthesis and release of [3H]man-PROT without affecting those of [14C]leu-PROT. The kinetics of synthesis and release of [3H]gal-PROT, although diminished, maintained linearity and increased in function of time, even in the presence of the antibiotics. Thus, the present results on glycoproteins from the pituitary gland are consistent with the previous conclusion for other mammalian glycoproteins that carbohydrate attachment occurs in several steps to molecules destined to be secreted. Addition of mannose (proximal glycosylation) is a co-translational event and that of galactose (distal glycosylation) is post-translational and can be designated as final stages in carbohydrate assembly, occurring close to the time of release. Furthermore, it has been demonstrated that the absence of the carbohydrate side chains of the pituitary glycoprotein does not prevent the intracellular transport of the protein and its export from the cell.

Cognitive factors in the dietary response of restrained and unrestrained eaters to manipulation of the fat content of a dish.

This study examined the dietary intake and rated internal state of 16 normal-weight young women following the manipulation of the actual or the presented fat and energy content of a test dish eaten at lunch. Half of the subjects were classified as restrained and half as unrestrained eaters. The test dish was either 2473 kJ (591 kcal) in its high-fat version or 1485 kJ (355 kcal) in its low-fat version, and was provided either with a correct or incorrect information about its fat content. All the intakes at the three meals during the following 8 h were covertly recorded in the laboratory, and internal state rated on four occasions. After the low-fat test dish presented as low-fat, unrestrained eaters increased their energy intake compared to that in other conditions. Restrained subjects did not exhibit this pattern and compensated for the missing energy in the low-fat test dish, compared to the high-fat test dish, only when they were informed that both dishes were high in fat. Irrespective of the information, both restrained and unrestrained subjects reported weaker sensations of hunger after the actual high-fat test dish than after the actual low-fat test dish whereas only restrained eaters reported stronger sensations of fullness. Thus, the influence of the cognitive factors on food intake and ratings of internal state is modulated by restrained eating behaviour.

Gastric distension, hunger and energy intake after balloon implantation in severe obesity.

OBJECTIVE: To investigate the interrelationships between satiety feelings, abdominal perception, energy intake and weight loss, related to the presence of an intragastric balloon. DESIGN: Randomized double blind study. SUBJECTS: 20 severely obese subjects, BMI > 40 kg/m2, randomly assigned either to receive an air filled balloon (n = 11) or to have a sham procedure (n = 9). All subjects had dietary counselling to help them follow a relatively low energy diet (60% of individual spontaneous intake). MEASUREMENTS: During biweekly visits, body weight was recorded, visual analogic scales for stomach distension, hunger and feeling of balloon presence were completed. Blood chemistry profiles were monitored once every 4 weeks. RESULTS: In the balloon group, the sensations related to the presence of the balloon and to abdominal distension dramatically increased after insertion, and plateaued during the next 4 weeks. Both feelings of presence and distension decreased thereafter, and after 10 weeks they were not significantly different from those of the sham balloon group. Hunger dramatically decreased to about 30% of initial rating in the first week, but slowly returned to the initial value by the 12th week. Hunger feelings were highly and negatively correlated with feelings of distension. During the same period, the sham balloon group continued to maintain the low energy intake, and did not register any feelings of distension or presence; hunger level did not differ from initial levels throughout the whole study. The energy intake and the rate of weight loss (8-9 kg) was similar in the two groups during the study, and were not correlated with the feelings of distension. CONCLUSION: This study showed that in severely obese subjects submitted to a restrictive diet, an intragastric balloon has a measurable but transient effect on the sensation of epigastric distension and is able to decrease feelings of hunger. Unfortunately, these effects were not associated with a lower energy intake or a higher rate of weight loss than the sham situation. Thus, the present study does not support the interest of such a balloon (500 ml, air filled) in the treatment of severe obesity.

Anatomic and physiologic heterogeneity in patients with syndrome X: an intravascular ultrasound study.

OBJECTIVES: We used intravascular ultrasound imaging of the epicardial vessels to assess coronary morphology, vasomotor response to exercise and exercise-vasomotion after beta-adrenoceptor blockade in patients with syndrome X. BACKGROUND: Syndrome X is defined as chest pain, abnormal exercise test results and normal coronary angiographic findings. Because of the limitations of coronary angiography, intravascular ultrasound was used to define coronary pathophysiology. METHODS: Thirty patients with syndrome X were studied with intravascular ultrasound imaging (30 MHz, 4.3F catheter) of all three major epicardial vessels. Supine arm exercise was performed during coronary imaging. Lumen area was assessed at rest and during peak exercise. The exercise-imaging protocol was repeated after loading with 0.1 mg/kg body weight of intravenous propranolol. RESULTS: Three morphologic groups were identified using intravascular ultrasound: normal coronary arteries (no plaque, intimal thickness < 0.25 mm, n = 12), atheromatous disease (mean [+/- SD] area stenosis 37.9 +/- 7.2%, n = 10) and marked intimal thickening (0.73 +/- 0.11 mm, n = 8). Patients with normal coronary arteries displayed a vasodilatory response to exercise (+16.9% area increase); patients with abnormal coronary arteries displayed a vasoconstrictive response to exercise (-17.4% in the group with plaque; -17.6% in the group with intimal thickening). Propranolol loading attenuated the vasodilatory response in the group with normal coronary arteries (+6.4% area increase) and attenuated the vasoconstrictive response in the two groups with abnormal coronary arteries (-8.0% in the group with plaque; -8.8% in the group with intimal thickening). CONCLUSIONS: Most patients with syndrome X have abnormal coronary arteries by intravascular ultrasound. Intravascular ultrasound identifies three distinct morphologic groups: normal coronary arteries, atheromatous plaque and intimal thickening. Exercise-vasomotion is normal in patients with syndrome X who have normal coronary arteries by ultrasound; patients with abnormal arteries (plaque or intimal thickening) have an abnormal (constrictive) response to exercise. Propranolol loading attenuates vasoreactivity in all subgroups, suggesting divergent therapeutic utility.

Effect of a covert fat dilution on the spontaneous food intake by lean and obese subjects.

Nine lean and nine obese subjects participated in two laboratory studies comparing the effects of a traditional high-fat dish (2.42 MJ and 49% as fat) and its convert fat-reduced version (1.53 MJ and 23% as fat) on subsequent food intake. Each version was consumed at the beginning of a free-choice lunch (experiment 1) or alone at lunch time (experiment 2). All subjects experienced both experiments. Three and 7 h after lunch, subjects were free to consume any of the items available in a vending machine. Food intake was measured directly. In experiment 1, by 8 h after lunch, mean cumulative energy intake (test dish included) was not different between the test dish conditions in both lean and obese subjects, and ad libitum energy intake (i.e. without test dish) was significantly higher under the low-fat than under the high-fat test dish condition. Thus, lean compensated 86% and obese 70% of the initial energy reduction. The cumulative fat intake (test dish included) was lower under the low-fat than under the high-fat dish condition for both weight groups. Nevertheless, the percentage of ad libitum energy intake derived from fat was significantly higher after the low-fat test dish in obese but not in lean subjects. In experiment 2, both weight groups maintained the energy and fat reduction. Thus, obese subjects did not respond differently to lean subjects to the fat and energy manipulation of the test dish, except for the percentage of fat in their diet. These results suggest that different ways of including fat-reduced foods into the habitual diet might have different effects on subsequent energy compensation.

Lipoprotein lipase gene polymorphisms: associations with hypertriglyceridemia and body mass index in obese people.

OBJECTIVE: To compare body mass index (BMI), lipid, lipoprotein and apolipoprotein concentrations according to the Hind III and Pvu II restriction polymorphisms of the LPL gene in obese subjects. DESIGN: Cross sectional study of anthropometric and lipid variables in relation to genetic factors. SETTING: Nutrition Outpatient Clinic of Bichat Hospital in Paris, France. SUBJECTS: 236 unrelated patients (162 women and 74 men) were selected on the basis of 120% of ideal body weight. MAIN OUTCOME MEASURES: Anthropometry (body mass index, waist to hip ratio), blood lipids and lipoproteins, determination of LPL Hind III and Pvu II genotypes. RESULTS: Digestion with Hind III generated two alleles, H1 (absence of cutting site) and H2 (presence of cutting site), with frequencies of 0.30 and 0.70 respectively. Digestion with Pvu II generated two alleles P1 and P2 with frequencies of 0.49 and 0.51 respectively. The Hind III polymorphism was significantly associated with body mass index (BMI) (P < 0.05). The H2H2 genotype was associated with hypertriglyceridemia: 68% of the hypertriglyceridemic subjects have the H2H2 genotype vs 43% of the normotriglyceridemic group (P < 0.05). Plasma triglyceride levels varied significantly among the Hind III genotypes, H2H2 genotype having the highest total and VLDL-triglyceride levels; the Hind III polymorphism also showed a significant association with HDL2-cholesterol. These associations were only seen in women and were not explained by the variations in BMI and age. No significant associations were found between lipid traits and Pvu II genotype. CONCLUSION: These results suggest that genetic variation in the LPL gene in obese subjects is associated with hypertriglyceridemia and possibly with a predisposition to obesity.