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Biomedical subjects

S St-Pierre

Publications and source records attributed to S St-Pierre.

At least 19 recordsLinked to original sources

Two new peptides to improve post-operative gastric ileus in dog.

Peptides can influence gastrointestinal motility, and from data obtained earlier in rats, we hypothesized that MTL-RP/Ghrelin, as well as CGRP receptor antagonist 8-37, could improve gastric post-operative ileus in dog. Dogs submitted to laparotomy were perfused with or saline or CGRP 8-37 or MTL-RP/Ghrelin on days 1-4 post-operatively while gastric emptying was estimated by measuring the postprandial increase in plasma acetaminophen ingested with a meal. As expected, in saline-treated animals the gastric emptying function was impaired post-operatively. The total amount of acetaminophen emptied (AUC over 150 min) on post-operative days 1-4 reached respectively 31+/-5%, 65+/-8%, 60+/-8% and 62+/-8% of the normal emptying capacity. CGRP antagonist increased the total emptying of acetaminophen to 52+/-5% on day 1, 95+/-2% on day 2 and 103+/-3% (P<0.05) on day 3. The delayed emptying of acetaminophen seen post-operatively in saline-treated animals could be completely reversed by MTL-RP/Ghrelin (P<0.01) whether it was given at 100 microg/kg on day 2 (102+/-7% of the normal emptying capacity), 4 microg/kg on day 3 (106+/-7%) or 20 microg/kg on day 4 (132+/-8%). As found earlier in rodents, CGRP receptor antagonist 8-37 as well as MTL-RP/Ghrelin are potent prokinetics to improve post-operative gastric ileus in dog.

Acetaminophen↗

Reduction of visceral adipose tissue during weight loss.

OBJECTIVE: The aims of the present study were to retrospectively: (1) compare how weight loss affects the reduction of adipose tissue from three different sites between men and women; and (2) to verify whether gender differences in the reduction of adipose tissue are influenced by changes in fat mass (FM) and initial levels of fat in different compartments. DESIGN: Double-blind randomized treatment with fenfluramine once daily coupled to a non-macronutrient specific energy restriction. SUBJECTS: Seventeen obese men (age 43.9+/-1.5 and body mass index (BMI) 34.3+/-0.7) and 17 obese women (age 41.2+/-1.2 and BMI 35.7+/-0.6). INTERVENTIONS: Subjects were given fenfluramine (60 mg) or placebo once daily and were also subjected to a non-macronurient specific energy restriction of -2.9 MJ/day (-700 kcal/day) for 15 weeks. RESULTS: Body weight, FM, fat-free mass (FFM), waist circumference, BMI, as well as visceral (VAT), subcutaneous abdominal (SAT) and thigh (TAT) adipose tissue were all significantly reduced. Men lost significantly more VAT (-41.6%) than SAT (-22.5%), or than TAT (-20.5%) while no site difference in fat loss was observed in women when changes were calculated as a percentage of initial levels. Men lost about twice as much fat from the VAT compartment than did women (P<0.05), even after having considered changes in FM as a potential covariate. In absolute values, TAT was reduced to a lesser extent in men than in women. However, when initial levels of respective fat depots were also taken into account, gender differences in VAT and TAT loss were no longer statistically significant. CONCLUSION: These results suggest that gender differences in VAT reduction during weight loss are independent of changes in FM. However, once initial levels of VAT are also taken into account, gender differences in the reduction of this tissue during weight loss are no longer apparent.

Adipose Tissue↗

Impact of high-intensity exercise on energy expenditure, lipid oxidation and body fatness.

OBJECTIVE: Two studies were conducted to assess the potential of an increase in exercise intensity to alter energy and lipid metabolism and body fatness under conditions mimicking real life. METHODS: Study 1 was based on the comparison of adiposity markers obtained in 352 male healthy adults who participated in the Québec Family Study who either regularly participated in high-intensity physical activities or did not. Study 2 was designed to determine the effects of high-intensity exercise on post-exercise post-prandial energy and lipid metabolism as well as the contribution of beta-adrenergic stimulation to such differences under a real-life setting. RESULTS: Results from Study 1 showed that men who regularly take part in intense physical activities display lower fat percentage and subcutaneous adiposity than men who never perform such activities, and this was true even if the latter group reported a lower energy intake (917 kJ/day, P<0.05). In Study 2, the high-intensity exercise stimulus produced a greater post-exercise post-prandial oxygen consumption as well as fat oxidation than the resting session, an effect which disappeared with the addition of propranolol. In addition, the increase in post-prandial oxygen consumption observed after the high-intensity exercise session was also significantly greater than that promoted by the low-intensity exercise session. CONCLUSION: These results suggest that high-intensity exercise favors a lesser body fat deposition which might be related to an increase in post-exercise energy metabolism that is mediated by beta-adrenergic stimulation.

Adipose Tissue↗

Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet--exercise intervention.

OBJECTIVE: : Sibutramine favors a negative energy balance and also has the potential to increase heart rate and blood pressure. We investigated if a progressive supervised sibutramine--diet--exercise clinical intervention could increase the body weight loss previously reported while minimizing the potential cardiostimulatory effects of this drug. DESIGN AND SUBJECTS: : The tri-therapy intervention was divided into two phases of 6 weeks each in which sibutramine (10 mg) was taken once daily by eight obese men (body mass index (BMI) between 30 and 40 kg/m(2)). Part A consisted of a dietary follow-up with an energy restriction, whereas in part B an aerobic exercise program combined with a low-fat diet was introduced. Systolic (SBP) and diastolic (DBP) blood pressure, resting heart rate (RHR) and body weight were measured every 2 weeks while body density, resting metabolic rate (RMR) and respiratory quotient (RQ) were determined before and after the intervention. RESULTS: : This clinical intervention produced a substantial body weight loss (-10.7 kg, P<0.01) which was about twice as much as other 12-week studies. In part A, both RHR (+4 beats/min) and DBP (+5 mmHg, P<0.01) were increased. However, after part B, RHR (-8 beats/min, P=0.02) and DBP (-3 mmHg, P<0.01) were significantly decreased. RMR was decreased at the end of the program but this effect did not persist after adjustments for fat-free mass. RQ was also reduced (-0.05, P<0.01) following the clinical tri-therapy. CONCLUSION: : In conclusion, these observations suggest that this clinical tri-therapy favored a satisfactory benefit--risk profile since it enhanced weight loss without inducing increases in heart rate and blood pressure or detrimental changes in RMR and substrate oxidation.

Adult↗

Difference in leptin response to a high-fat meal between lean and obese men.

The aim of this study was to compare the leptin responses to a high-fat meal in lean and obese men, and to investigate whether the net leptin response (area under the incremental curve) after the meal was related to the thermic effect of food (TEF). Blood samples were collected after an overnight fast and every 2 h for 8 h after a high-fat breakfast (60 g of fat/m(2) body surface area) in 12 lean and 12 obese men for determination of glucose, insulin and leptin. The TEF was calculated as postprandial energy expenditure minus fasting energy expenditure, as measured by indirect calorimetry. Fasting plasma glucose levels were similar in lean and obese men, and increased in the same way after the meal. Fasting and postprandial plasma insulin concentrations were significantly greater in obese than in lean men (P<0.01 and P<0.05 respectively). Accordingly, obese men showed a significantly higher net insulin response than lean subjects (P<0.001). Fasting plasma leptin levels were greater in obese than in lean men (P<0.001). After the meal, plasma leptin increased significantly in lean men, whereas it decreased in obese men (group by time interaction, P<0.01). The net response of leptin was greater in lean than in obese men, but this did not reach statistical significance (P=0.07). Moreover, the TEF was similar in the two groups. No significant relationship was observed between either the net insulin response or the net leptin response after the high-fat meal and the TEF of lean subjects (-0.05 <r<0.31). In obese men, the net response of insulin was correlated significantly with TEF (r=0.70, P<0.05), whereas the net response of leptin was not (r=-0.40). These results suggest that obesity is related to an impaired regulation of leptin by insulin, since leptin levels increased in lean men but decreased in obese men following a high-fat meal. Moreover, the fact that the postprandial leptin responses of both lean and obese men were not significantly related to the TEF suggests that the ob gene product is probably not acutely involved in the control of this energy expenditure component in humans.

Adult↗

Evidence for the existence of adaptive thermogenesis during weight loss.

The present study was performed to further investigate the adaptive component of thermogenesis that appears during prolonged energy restriction. Fifteen obese men and twenty obese women underwent a 15-week weight-loss programme. During this programme, body weight and composition as well as resting energy expenditure (REE) were measured at baseline, after 2 and 8 weeks of energy restriction (-2929 kJ/d) and drug therapy (or placebo), and finally 2-4 weeks after the end of the 15-week drug therapy and energy restriction intervention, when subjects were weight stable. Regression equations were established in a control population of the same age. These equations were then used to predict REE in obese men and women at baseline, after 2 and 8 weeks, as well as after the completion of the programme. In both men and women body weight and fat mass were significantly reduced in all cases) while fat-free mass remained unchanged throughout the programme. At baseline, REE predicted from the regression equation was not significantly different from the measured REE in men, while in women the measured REE was 13 % greater than predicted. After 2 weeks of energy restriction, measured REE had fallen by 469 and 635 kJ/d more than predicted and this difference reached 963 and 614 kJ/d by week 8 of treatment in men and women respectively. Once body-weight stability was recovered at the end of the programme, changes in REE remained below predicted changes in men (-622 kJ/d). However, in women changes in predicted and measured REE were no longer different at this time, even if the women were maintaining a reduced body weight. In summary, the present results confirm the existence of adaptive thermogenesis and give objective measurements of this component during weight loss in obese men and women, while they also emphasize that in women this component seems to be essentially explained by the energy restriction.

Adaptation, Physiological↗

Effect of a low-glycaemic index--low-fat--high protein diet on the atherogenic metabolic risk profile of abdominally obese men.

It has been suggested that the current dietary recommendations (low-fat-high-carbohydrate diet) may promote the intake of sugar and highly refined starches which could have adverse effects on the metabolic risk profile. We have investigated the short-term (6-d) nutritional and metabolic effects of an ad libitum low-glycaemic index-low-fat-high-protein diet (prepared according to the Montignac method) compared with the American Heart Association (AHA) phase I diet consumed ad libitum as well as with a pair-fed session consisting of the same daily energy intake as the former but with the same macronutrient composition as the AHA phase I diet. Twelve overweight men (BMI 33.0 (sd 3.5) kg/m2) without other diseases were involved in three experimental conditions with a minimal washout period of 2 weeks separating each intervention. By protocol design, the first two conditions were administered randomly whereas the pair-fed session had to be administered last. During the ad libitum version of the AHA diet, subjects consumed 11695.0 (sd 1163.0) kJ/d and this diet induced a 28 % increase in plasma triacylglycerol levels (1.77 (sd 0.79) v. 2.27 (sd 0.92) mmol/l, P<0.05) and a 10 % reduction in plasma HDL-cholesterol concentrations (0.92 (sd 0.16) v. 0.83 (sd 0.09) mmol/l, P<0.01) which contributed to a significant increase in cholesterol:HDL-cholesterol ratio (P<0.05), this lipid index being commonly used to assess the risk of coronary heart disease. In contrast, the low-glycaemic index-low-fat-high-protein diet consumed ad libitum resulted in a spontaneous 25 % decrease (P<0.001) in total energy intake which averaged 8815.0 (sd 738.0) kJ/d. As opposed to the AHA diet, the low-glycaemic index-low-fat-high-protein diet produced a substantial decrease (-35 %) in plasma triacylglycerol levels (2.00 (sd 0.83) v. 1.31 (sd 0.38) mmol/l, P<0.0005), a significant increase (+1.6 %) in LDL peak particle diameter (251 (sd 5) v. 255 (sd 5) A, P<0.02) and marked decreases in plasma insulin levels measured either in the fasting state, over daytime and following a 75 g oral glucose load. During the pair-fed session, in which subjects were exposed to a diet with the same macronutrient composition as the AHA diet but restricted to the same energy intake as during the low-glycaemic index-low-fat-high-protein diet, there was a trend for a decrease in plasma HDL-cholesterol levels which contributed to the significant increase in cholesterol:HDL-cholesterol ratio noted with this condition. Furthermore, a marked increase in hunger (P<0.0002) and a significant decrease in satiety (P<0.007) were also noted with this energy-restricted diet. Finally, favourable changes in the metabolic risk profile noted with the ad libitum consumption of the low-glycaemic index-low-fat-high-protein diet (decreases in triacyglycerols, lack of increase in cholesterol:HDL-cholesterol ratio, increase in LDL particle size) were significantly different from the response of these variables to the AHA phase I diet. Thus, a low-glycaemic index-low-fat-high-protein content diet may have unique beneficial effects compared with the conventional AHA diet for the treatment of the atherogenic metabolic risk profile of abdominally obese patients. However, the present study was a short-term intervention and additional trials are clearly needed to document the long-term efficacy of this dietary approach with regard to compliance and effects on the metabolic risk profile.

Analysis of Variance↗

Oral delivery of glucagon-like peptide-1 in a modified polymer preparation normalizes basal glycaemia in diabetic db/db mice.

AIMS/HYPOTHESIS: The insulinotropic hormone, glucagon-like peptide-1 has been proposed for the treatment of patients with Type II (non-insulin-dependent) diabetes mellitus. As glucagon-like peptide-1 is rapidly cleaved at L-ala2 by dipeptidylpeptidase IV, D-ala2-glucagon-like peptide-1 was synthesized and shown to have dipeptidylpeptidase IV resistance in vitro and enhanced bioactivity in mice during an oral glucose challenge. The actions of D-ala2-glucagon-like peptide-1 were, however, lost within 4 h of injection, thus necessitating frequent and invasive treatment if it is to be used therapeutically. To circumvent this problem, a microsphere of D-ala2-glucagon-like peptide-1 that could be given orally was developed. METHODS: We encapsulated D-ala2-glucagon-like peptide-1 in poly(lactide-co-glycolide)-COOH with olive oil as a filler, using phase inversion. The microspheres were tested in vivo by oral gavage in mice at t = 0 h followed by repeated oral glucose tolerance tests at t = 0, 4 and 8 h. RESULTS: The D-ala2-glucagon-like peptide-1-microspheres lowered the glycaemic response to the 4 h oral glucose challenge in both normal CD1 and diabetic db/db mice, by 41 +/- 12% (p <0.001) and 27 +/- 5% (p < 0.001), respectively and by 19 +/- 11% (p < 0.05) and 28 +/- 4% (p < 0.001), respectively during the 8-h test. At 4 h after the oral gavage, basal glycaemia in the diabetic mice was reduced from 13 +/- 1 mmol/l to 10 +/- 1 mmol/l and was reduced further 8h after treatment from 12 +/- 1 mmol/l to 8 +/- 1 mmol/l (p < 0.05). Giving D-ala2-glucagon-like peptide-1 alone orally had no effect on glycaemia. CONCLUSION/INTERPRETATION: The data presented here suggest that a similar microsphere preparation could be useful in the delivery of glucagon-like peptide-1 to patients with Type II diabetes.

3-O-Methylglucose↗

Digestive motor effects and vascular actions of CGRP in dog are expressed by different receptor subtypes.

Calcitonin gene-related peptide (CGRP) is a 37 AA peptide localized in blood vessels and nerves of the GI tract. Activation of CGRP receptors (subtypes 1 or 2) usually induces vasodilation and/or muscle relaxation, but its effects in dog and on gastroduodenal motility are still unclear. This study looked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GI motility (interdigestive and postprandial), and 2) on hemodynamy, in conscious dogs. During the interdigestive period, the infusion of CGRP1-37 (200 pmol/kg/h) or CGRP8-37 (2000 pmol/kg/h) did not modify the duration of the migrating motor complex nor the release nor the motor action of plasma motilin. The gastric emptying of a solid meal (15 g meat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T12: 78 +/- 7.3 versus 50 +/- 4.3 min; P < 0.01) and this effect was reversed by the antagonist CGRP8-37. CGRP1-37 significantly (P < 0. 01) diminished arterial pressures (118 +/- 1.6/64 +/- 1.4 vs. 125 +/- 1.4/75 +/- 1.2 mmHg with saline) and accelerated the basal cardiac rhythm (110 +/- 1.4 versus 83 +/- 1.6 beats/min). However, CGRP8-37 failed to block the cardiovascular effects of CGRP1-37. In dog, CGRP could influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-1 receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype.

Animals↗

Neural and muscular receptors for motilin in the rabbit colon.

Motilin receptors were classically recognized in the gastroduodenal area, where they help to regulate interdigestive motility. More recently, motilin receptors were identified in the colon where their biologic significance remains unclear. We aimed here to characterize the motilin receptors of the rabbit colon. Distal colon and duodenum were obtained from sacrificed rabbits. Tissues homogenized by Polytron were submitted to differential centrifugation to obtain neural synaptosomes or smooth muscle plasma membranes enriched solutions. Motilin binding to these membranes was determined by the displacement of (125)I MOT by the native peptide MOT 1-22, or by peptide analogues MOT 1-12 [CH(2)NH](10-11) or GM-109 and by erythromycin derivative GM-611. Motilin binding capacity was maximum in colon nerves (49.5 +/- 6.5 fmol/mg protein vs. 19.9 +/- 2.5 in colon muscles or 9.4 +/- 2.8 and 6.6 +/- 1.2 in duodenal muscles and antral nerves respectively); all tissues expressed similar affinity for MOT 1-22, and the motilin agonist GM-611 bound equally to neural or muscle tissues from the rabbit colon; the synthetic antagonist MOT 1-12 [CH(2)NH](10-11) showed greater affinity for colon nerves than for colon muscles (plC50: 7.23 +/- 0.07 vs. 6.75 +/- 0.03). Similar results were obtained with the peptide antagonist GM-109; receptor affinity toward MOT 1-12 [CH(2)NH(10-11)] was always five times superior in neural tissues, whether they came from the colon or the antrum, than in muscle tissues, whether they were obtained from colon or from duodenum. Motilin receptors are found in very high concentration in nerves and in muscles from rabbit colon; specific motilin receptor subtypes are identified in nerves (N) and muscles (M) of the rabbit colon; N and M receptor subtypes seem independent of the organ location.

Animals↗

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↗

Motilin receptors in the human antrum.

Motilin is an intestinal peptide that stimulates contraction of gut smooth muscle. The motilin receptor has not been cloned yet, but motilin-receptor agonists appear to be potent prokinetic agents for the treatment of dysmotility disorders. The aim of this study was to determine neural or muscular localization of motilin receptors in human upper gastrointestinal tract and to investigate their pharmacological characteristics. The binding of (125)I-labeled motilin to tissue membranes prepared from human stomach and duodenum was studied; rabbit tissues were used for comparison. Solutions enriched in neural synaptosomes or in smooth muscle plasma membranes were obtained. Various motilin analogs were used to displace the motilin radioligand from the various tissue membranes. The highest concentration of human motilin receptors was found in the antrum, predominantly in the neural preparation. Human motilin receptors were sensitive to the NH(2)-terminal portion of the motilin molecule, but comparison with rabbit showed that both species had specific affinities for various motilin analogs [i.e., Mot-(1-9), Mot-(1-12), Mot-(1-12) (CH(2)NH)(10-11), and erythromycin]. Motilin receptors obtained from synaptosomes or muscular plasma membranes of human antrum expressed different affinity for two motilin-receptor agonists, Mot-(1-12) and Mot-(1-12) (CH(2)NH)(10-11), suggesting that they correspond to specific receptor subtypes. We conclude that human motilin receptors are located predominantly in nerves of the antral wall, are functionally (and probably structurally) different from those found in other species such as the rabbit, and express specific functional (and probably structural) characteristics dependent on their localization on antral nerves or muscles, suggesting the existence of specific receptor subtypes, potentially of significant physiological or pharmacological relevance.

Animals↗

Characterization of neuropeptide Y-mediated corticotropin-releasing factor synthesis and release from human placental trophoblasts.

Neuropeptide Y (NPY) is a CRF secretagogue for human placental cells in culture. We have studied the involvement of intracellular calcium and calcium-dependent signaling in the NPY-induced CRF release in trophoblastic cells. The incubation of trophoblasts with NPY for 3 and 8 h led to a dose-dependent increase in CRF secretion. Also, NPY stimulated synthesis of this peptide hormone upon an 8-h incubation period. BIBP3226, a selective Y1 receptor antagonist, and pertussis toxin (PTX) eliminated these effects. NPY-stimulated CRF secretion was mostly prevented by loading cells with BAPTA-AM, suggesting that elevation of intracellular calcium is responsible for the increase of CRF secretion. However, this calcium chelator had no effect on CRF synthesis. Furthermore, U-73122, a phospholipase C-betas (PLC) inhibitor or xestospongin C, an inositol triphosphate receptor (InsP3-R) blocker, have partially prevented the effect of NPY on CRF synthesis and secretion. Therefore, the increase in CRF synthesis and secretion rely in part on the release of calcium from intracellular store. Interestingly, SKF 96365, an inhibitor of store operated calcium (SOC) influx, also partially blocked the NPY stimulatory effect on CRF release but not its synthesis, suggesting that calcium influx is also involved in this stimulation. In the syncytiotrophoblast, known to possess a NPY-activated protein kinase C (PKCs) activity, NPY also stimulated calcium calmodulin kinase II (CaMKII) and extracellular regulated kinase (ERK1/2) activities. In the present study, we observed that bisindolylmaleimide (BIM), a nonspecific PKCs inhibitor partially prevented the NPY-induced CRF release. On the other hand, autocamtide-2 related inhibitory peptide (AIP), a CaMKII inhibitor, prevented most of the stimulatory effect of NPY on both CRF synthesis and release. Go6976, an inhibitor of the conventional and mu PKCs and PD 098059, an inhibitor of the ERK cascade, had no effect on neither CRF synthesis nor release. Altogether, these results support a Y1 receptor-mediated PTX-sensitive induction on CRF synthesis and release by NPY from human placental trophoblasts. The stimulation of CRF synthesis by NPY seems to depend mainly on a PLC-beta to InsP3-R axis and on CaMKII activity. Also, the release of CRF depends on the PLC-beta to InsP3-R axis and CaMKII activity but also entails the participation of a calcium-independent PKCs.

Arginine↗

Fasting insulin levels influence plasma leptin levels independently from the contribution of adiposity: evidence from both a cross-sectional and an intervention study.

The aim of the present investigation was to determine whether leptinemia is only a reflection of the status of fat stores or if insulinemia has a significant influence over leptin levels. Study 1 focused on the association between fasting plasma insulin and leptin in subjects of the Quebec Family Study who were first classified as either high- or low-insulin individuals and were then individually matched on the basis of fat mass (FM). In Study 2, 19 men and 23 women took part in a 15-week weight loss program that consisted of drug therapy (fenfluramine, 60 mg/day) or placebo coupled to an energy-restricted diet (-2930 kJ/day). Body weight, FM, and fat-free mass (assessed by underwater weighing) as well as visceral and sc abdominal and mid-thigh adipose tissue measured by computed tomography were assessed before and after weight loss. Blood samples were drawn and analyzed for fasting plasma insulin and leptin before and after weight loss. In Study 1, significant positive associations were noted between log10 transformed fasting insulin and leptin in both men (r = 0.55, P < 0.0001) and women (r = 0.48, P < 0.0001). Moreover, after having carefully matched high-insulin to low-insulin individuals on the basis of FM, significantly lower leptin levels were observed in the low-insulin groups, in men (5.5 vs. 8.1 ng/mL, P < 0.05) as well as in women (18.7 vs. 24 ng/mL, P < 0.05). Results from Study 2 showed significant reductions of body weight, FM, fat-free mass, visceral abdominal tissue, sc abdominal tissue, and mid-thigh adipose tissue levels in men and women in response to the weight loss protocol. Moreover, the decrease in fasting plasma insulin was the only significant correlate of changes in fasting plasma leptin levels during weight loss, even after corrections for changes in FM in both men (r = 0.50, P < 0.05) and women (r = 0.46, P < 0.05). These results suggest that in a population characterized by a wide range of adiposity hyperinsulinemia has the potential to modulate leptin levels beyond what can be explained by total adiposity. Moreover, this relation also seems to exist in a dynamic setting (i.e. during weight loss) because changes in insulin were independent predictors of the changes in leptinemia in both men and women after correction for changes in FM.

Adipose Tissue↗

Screening level dose assessment of aquatic biota downstream of the Marcoule nuclear complex in southern France.

Aquatic biota in the Rhone River downstream of the Marcoule nuclear complex in France are exposed to natural sources of radiation and to radioactivity released from the Marcoule complex. A simple conservative screening level model was used to estimate the range of concentrations in aquatic media (water, sediments, and aquatic organisms) of both artificial and natural radionuclides and the consequent absorbed (whole body) dose rates for aquatic organisms. Five categories of aquatic organisms were studied, namely, submerged aquatic plants (phanerogam), non-bottom-feeding fish, bottom-feeding fish, mollusca, and fish-eating birds. The analysis was based on the radionuclide concentrations reported in four consecutive annual radioecological monitoring reports published by French agencies with nuclear regulatory responsibilities. The results of this assessment were used to determine, qualitatively, the magnitude of any potential health impacts on each of the five categories of aquatic organisms studied. The range of dose rate estimates ranged over three orders of magnitude, with maximum dose rates estimated to be in the order of 1 to 10 microGy h(-1). These maximum dose rates are a factor 40 or more below the international guideline intended to ensure the protection of aquatic populations (about 400 microGy h(-1)), and a factor ten or more below the level which may trigger the need for a more detailed evaluation of potential ecological consequences to the exposed populations (about 100 microGy h(-1)). As a result, chronic levels of radioactivity, artificial and natural, measured in aquatic media downstream of Marcoule are unlikely to result in adverse health impacts on the categories and species of aquatic organisms studied. Thus, based on the screening level analysis discussed in this paper, a more detailed evaluation of the dose rates does not appear to be warranted.

Alpha Particles↗

Effects of red pepper on appetite and energy intake.

Two studies were conducted to investigate the effects of red pepper (capsaicin) on feeding behaviour and energy intake. In the first study, the effects of dietary red pepper added to high-fat (HF) and high-carbohydrate (HC) meals on subsequent energy and macronutrient intakes were examined in thirteen Japanese female subjects. After the ingestion of a standardized dinner on the previous evening, the subjects ate an experimental breakfast (1883 kJ) of one of the following four types: (1) HF; (2) HF and red pepper (10 g); (3) HC; (4) HC and red pepper. Ad libitum energy and macronutrient intakes were measured at lunch-time. The HC breakfast significantly reduced the desire to eat and hunger after breakfast. The addition of red pepper to the HC breakfast also significantly decreased the desire to eat and hunger before lunch. Differences in diet composition at breakfast time did not affect energy and macronutrient intakes at lunch-time. However, the addition of red pepper to the breakfast significantly decreased protein and fat intakes at lunch-time. In Study 2, the effects of a red-pepper appetizer on subsequent energy and macronutrient intakes were examined in ten Caucasian male subjects. After ingesting a standardized breakfast, the subjects took an experimental appetizer (644 kJ) at lunch-time of one of the following two types: (1) mixed diet and appetizer; (2) mixed diet and red-pepper (6 g) appetizer. The addition of red pepper to the appetizer significantly reduced the cumulative ad libitum energy and carbohydrate intakes during the rest of the lunch and in the snack served several hours later. Moreover, the power spectral analysis of heart rate revealed that this effect of red pepper was associated with an increase in the ratio sympathetic: parasympathetic nervous system activity. These results indicate that the ingestion of red pepper decreases appetite and subsequent protein and fat intakes in Japanese females and energy intake in Caucasian males. Moreover, this effect might be related to an increase in sympathetic nervous system activity in Caucasian males.

Adult↗

Immuno-electron microscopic study of differential localization of motilin and serotonin in the rabbit duodenal epithelium.

A guinea pig antibody against rabbit motilin was generated to study the localization of motilin-containing cells in the rabbit small intestine with special reference to the co-localization of motilin and serotonin. A pre- and post-embedding technique for immuno-electron microscopy was used; duodenal sections were stained with either motilin or serotonin in the pre-embedding DAB-nickel reaction, followed by subsequent staining of ultrathin sections of positive cells with either motilin or serotonin in the post-embedding immunogold reaction. Samples were divided into four groups: 1) pre-motilin, post-motilin, 2) pre-motilin, post-serotonin, 3) pre-serotonin, post-serotonin, and 4) pre-serotonin, post-motilin. Motilin-containing cells in the rabbit duodenum were characterized by round granules (395.3 +/- 66.1 nm in diameter) with medium electron density, located basally or in the perinuclear cytoplasm. In contrast, serotonin-containing cells were characterized by round to pleomorphic secretory granules (344.5 +/- 90.5 nm in diameter with electron dense cores and prominent halos. In motilin-containing cells, massive aggregations of immunogold particles reacted to motilin occurred over secretory granules. A few immunogold particles scattered diffusely over the cytoplasm reacted to serotonin; however, this reaction appeared to be background staining because the density was not changed if the section was treated by preabsorption. In serotonin-containing cells, immunogold particles reacted to serotonin were aggregated over the secretory granules and a large number of gold particles were scattered diffusely at the extragranular cytoplasm; however, very few or no immunogold particles were observed within the cells which reacted to motilin. Results of the present study indicate that motilin and serotonin are not co-localized in the epithelial endocrine cells of the rabbit intestine.

Animals↗

Effects of red pepper added to high-fat and high-carbohydrate meals on energy metabolism and substrate utilization in Japanese women.

The effects of dietary red pepper added to high-fat (HF) and high-carbohydrate (HC) meals on energy metabolism were examined in thirteen Japanese female subjects. After ingesting a standardized dinner on the previous evening, the subjects took an experimental breakfast (1883 kJ) under the following four conditions: HF meal, HF and red-pepper (10 g) meal, HC meal, or HC and red-pepper meal. Palatability of the experimental meals was measured immediately after the meals. Expired air was collected before and for 210 min after the meal to determine energy expenditure and macronutrient oxidation. Diet-induced thermogenesis was significantly higher after the HC meals than after the HF meals. Lipid oxidation was significantly lower and carbohydrate oxidation was significantly higher after the HC meals than after the HF meals. Addition of red pepper to the experimental meals significantly increased diet-induced thermogenesis and lipid oxidation, particularly after the HF meal. On the other hand, carbohydrate oxidation was significantly decreased by the addition of red pepper to the experimental meals. Addition of red pepper to the HC meal increased the perceived oiliness of the meal to the same level as that of the HF meals. These results indicate that red pepper increases diet-induced thermogenesis and lipid oxidation. This increase in lipid oxidation is mainly observed when foods have a HF content whereas the increase in the perceived oiliness of the meal was found under the HC meal conditions.

Adult↗