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Biomedical subjects

A Nadeau

Publications and source records attributed to A Nadeau.

At least 19 recordsLinked to original sources

Genetic aspects of susceptibility to obesity and related dyslipidemias.

Obesity has a multifactorial origin. However, although environmental variables undoubtedly play a role in the development of obesity, it is now clear that genetic variation is also involved in the determination of an individual's susceptibility to body fat accumulation. In addition, it is also widely accepted that obesity is not a single homogeneous phenotype. It is also heterogeneous regarding its causes and metabolic complications. The regional distribution of body fat appears to be an important correlate of the metabolic complications that have been related to obesity. Due to their higher accumulation of abdominal fat, men are generally more at risk for the metabolic complications of obesity than women whereas some obese women, with large gluteal-femoral adipose depots may have a cosmetic problem which may not necessarily require medical intervention. Several studies have been conducted to understand the mechanisms by which abdominal obesity is related to diabetes, hypertension and cardiovascular disease. It appears that the increased risk of abdominal obesity is the result of complex hormonal and metabolic interactions. Studies in genetic epidemiology have shown that both total body fatness and the regional distribution of body fat have a significant genetic component. Standardized intervention studies using an identical twin design have shown that individuals that have the same genetic background tend to show similar changes in body fat and in plasma lipoprotein levels when exposed to standardized caloric excess or energy restriction. Finally, although abdominal obesity is a significant risk factor for cardiovascular disease, not every abdominal obese subject will experience metabolic complications, suggesting that some obese individuals may be more susceptible than others. Variation in several genes relevant to lipid and lipoprotein metabolism may alter the relation of abdominal obesity to dyslipoproteinemias. Abdominal obesity should therefore be considered as a factor that exacerbates an individual's susceptibility to cardiovascular disease.

Adipose Tissue

Heterogeneous glycaemic and insulinaemic responses to oral glucose in non-diabetic men: interactions between duration of obesity, body fat distribution and family history of diabetes mellitus.

The interaction between environmental and genetic factors in the alterations of glucose-insulin homeostasis was studied in 104 non-diabetic men. Family history of diabetes mellitus was used as an index of genetic predisposition to diabetes. Body composition was measured by underwater weighing whereas subcutaneous and visceral adipose tissue areas were measured at the abdominal and femoral levels by computed tomography. The sample was first divided into two groups. The first group included subjects with "normal" glycaemic and insulinaemic responses during a 75 g oral glucose tolerance test. The second group was composed of subjects either with a high glucose response or high insulin response or both. Men included in the second group were different from the "normal" subjects for almost all body fatness variables. They also presented a prevalence of a positive family history of diabetes which was significantly higher than "normal" subjects. The second group was then divided into three distinct subgroups based on insulin and glucose responses of the subjects during the oral glucose tolerance test. Subjects with high insulin but "normal" glucose responses were characterized by significantly higher levels of total body fat and deep abdominal adipose tissue when compared to the "normal" group (p less than 0.05). Men with both high insulinaemic and glycaemic responses displayed higher body fatness values and higher deep and subcutaneous abdominal adipose tissue areas (p less than 0.05) in comparison with "normal" subjects. They also had a higher body mass index at age 20 years than control subjects and subjects with high insulin but "normal" glucose responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Is body fat loss a determinant factor in the improvement of carbohydrate and lipid metabolism following aerobic exercise training in obese women?

Thirty-one obese, premenopausal women aged 35.4 +/- 5.1 (SD) years exercised for 90 minutes at approximately 55% of maximal aerobic power (VO2max) four to five times a week for a period of 6 months. The training program induced a significant increase in VO2max (P < .001) and significant improvements in carbohydrate and lipid metabolism, as reflected by decreased plasma insulin (INS) concentrations measured in the fasting state and after glucose (GLU) ingestion (INS area, P < .001), by reduced plasma cholesterol (C) and low-density lipoprotein cholesterol (LDL-C) levels (P < .001), and by increased ratios of high-density lipoprotein cholesterol (HDL-C)/LDL-C and HDL2-C/HDL3-C (P < .05 and P < .001, respectively). Changes in body fat mass were positively associated with changes in the INS area/GLU area ratio (r = .49, P < .05) and with changes in very-low-density lipoprotein triglycerides ([VLDL-TG] r = .49, P < .05). Furthermore, changes in the INS area were positively associated with changes in VLDL-TG (r = .51, P < .05). Although no significant mean change in body composition was observed, important individual variation was noted. Twenty women showed a reduction in body fat mass (mean reduction, 2.63 +/- 2.2 kg), whereas 11 women showed an increase in adipose mass (mean increase, 2.79 +/- 2.36 kg). Comparable increases in VO2max were observed between the two groups. The group that showed a decrease in body fat mass with exercise also had significant improvements in carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Adrenodemedullation does not impair the beneficial effect of physical training in streptozotocin-diabetic rats.

This study was designed to ascertain if the improvement in glucose homeostasis found in diabetic animals submitted to physical training is due to an increased secretion of epinephrine by the adrenal medullae. Male Wistar rats were surgically adrenodemedullated (ADM group) or sham-operated (SHAM group). After a 3-week recovery period, a bolus of streptozotocin (40 mg/kg) was injected intravenously (IV), and the animals presenting 1 week later with a blood glucose value between 14 and 22 mmol/L were retained in the protocol and randomly assigned to a sedentary (SHAM-DS and ADM-DS) or trained (SHAM-DT and ADM-DT) group. Physical training was done on a treadmill according to a 10-week progressive program. An IV glucose tolerance test (0.5 g/kg) was performed in previously cannulated rats, 64 hours after the last bout of exercise. Pancreatic insulin and glucagon content was also determined. In sedentary diabetic rats, adrenodemedullation had no effect on plasma glucose, insulin, or glucagon levels, neither in the basal state nor following the glucose load. Basal glucose levels were diminished by training in both SHAM (16.1 +/- 1.5 v 21.8 +/- 0.4 mmol/L; P less than .01) and ADM (12.4 +/- 1.7 v 21.1 +/- 1.2 mmol/L; P less than .01) groups, with values lower in ADM-DT than in SHAM-DT rats (P less than .05). After glucose loading, the glucose levels were significantly lower (P less than .01) throughout the test in both SHAM-DT and ADM-DT rats than in their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla

Physical training increases beta-adrenoceptor density and adenylate cyclase activity in high-oxidative skeletal muscle of diabetic rats.

The effects of physical training on beta-adrenergic-receptor density (Bmax) and adenylate cyclase (AC) activity in soleus muscles (type I) and the deep red portion (type IIa) and superficial white portion (type IIb) of vastus lateralis muscles in diabetic rats were investigated. Rats were rendered diabetic with streptozotocin ([STZ] 45 mg/kg intravenously [IV]) and were either kept sedentary ([SD] n = 12) or submitted to a progressive 10-week treadmill running program ([TD] n = 13). A group of normal sedentary rats served as controls ([SC] n = 13). Plasma glucose levels were increased in SD rats in comparison with SC rats (21.3 +/- 1.4 mmol/L v 7.7 +/- 0.2; mean +/- SE, P < .001), but levels were partially reversed to normal by training (10.7 +/- 1.7; P < .01 v SD). The gastrocnemius nicotinamide adenine dinucleotide (NAD)-isocitrate dehydrogenase (ICDH) activity was significantly increased in TD rats in comparison to SC or SD rats (P < .001). The Bmax and antagonist affinity (Kd) determined with 125iodocyanopindolol (ICYP) were not affected by diabetes in any of the three types of muscle. In type I muscle, TD rats showed a significant 67% increase in Bmax compared with that of SD rats (TD 26.7 +/- 2.0 v SD 16.0 +/- 1.0; P < .001). In type IIa muscle, Bmax was significantly higher by 68% in TD rats as compared with SD rats (TD 16.5 +/- 1.7 v SD 9.8 +/- 0.9 fmol/mg protein; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases

Partial correction of impaired creatine kinase activity in diabetic rat heart by physical training.

The effect of physical training on total creatine kinase (CK), CK-MM, and CK-MB isoenzyme activity was studied in hearts of diabetic and control rats. Diabetes was induced with streptozotocin (50 mg/kg), and only rats with blood glucose levels between 14 and 22 mmol/L 1 week later were kept in the protocol. Exercise training was performed on a treadmill in a progressive 10-week program. Physical training did not induce any significant changes in plasma glucose or insulin levels in diabetic rats. Total CK, CK-MM, and CK-MB activity was decreased in diabetic rat heart by 27%, 22%, and 56%, respectively. Physical training did not induce any important changes in CK activity in heart of nondiabetic rats. However, in diabetic rat heart, training increased total CK activity by 13%, CK-MM activity by 12%, and CK-MB activity by 31%. We conclude that the decrease in cardiac CK activity observed in chronic experimental diabetes mellitus can be partly alleviated by a program of physical training. This may be one of the mechanisms whereby physical conditioning improves cardiac function in experimental diabetes.

Analysis of Variance

A study of some potential correlates of the hypotensive effects of prolonged submaximal exercise in normotensive men.

This study was undertaken (1) to examine the relation of plasma catecholamine and insulin levels to the blood pressure response during and after submaximal exercise, (2) to verify whether the blood pressure response to an epinephrine infusion is associated with the blood pressure response to a prolonged submaximal exercise, and (3) to study some potential correlates of the hypotensive effect of prolonged aerobic exercise. Nine normotensive young men (mean age 22.0 +/- 1.4 years) were subjected to a 1-h epinephrine infusion protocol and a 1-h submaximal exercise test on a cycle ergometer. The two tests were performed 1 week apart. The physiological and hormonal responses observed during the submaximal exercise test were generally greater than those observed during the epinephrine infusion test. Blood pressure responses in both tests showed no significant association with changes in plasma insulin levels. Changes in plasma norepinephrine concentration were positively correlated with changes in systolic blood pressure during the submaximal exercise test but not during the epinephrine infusion. Results also showed that the blood pressure response to epinephrine infusion was not correlated with the blood pressure response to submaximal exercise. However, post-exercise and post-infusion systolic blood pressure responses (differences between "post-test" and "resting" values) were significantly associated (r = 0.81, p less than 0.01). In addition, a significant hypotensive effect of submaximal exercise was observed for both systolic and diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Increased resting metabolic rate and lipid oxidation in exercise-trained individuals: evidence for a role of beta-adrenergic stimulation.

This study investigated the contribution of beta-adrenergic stimulation to the increase in resting metabolic rate (RMR) and lipid oxidation observed in exercise-trained individuals. Nine trained and eight sedentary men were subjected to two testing sessions, during which these variables were measured before and for 3 h after the oral administration of propranolol or placebo. As expected, RMR and lipid oxidation were significantly higher in the trained subjects before the administration of propranolol and throughout the placebo test in comparison with sedentary controls. A significant decrease in RMR and lipid oxidation was induced by propranolol in the trained subjects, whereas no change was observed in the untrained group, and this effect of propranolol was sufficient to abolish the difference between the two groups at baseline and under the placebo condition. Propranolol also induced a significant reduction in heart rate and systolic blood pressure, but the response was comparable in the two groups. In conclusion, the results of this study show that beta-adrenergic stimulation is involved in the increase in RMR and lipid oxidation observed in highly trained individuals. Moreover, the absence of a training-propranolol interaction effect on heart rate and systolic blood pressure suggests the existence of some dissociation between the metabolic and cardiovascular effects of prolonged exercise training.

Adult

Baroreflex regulation of forearm vascular resistance after exercise in hypertensive and normotensive humans.

The mechanisms underlying the antihypertensive period following a bout of exercise are not well understood. We examined the aftereffects of exercise on the linear relationship between forearm vascular resistance (FVR) and estimated central venous pressure (CVP) during leg raising and lower body negative pressure to determine whether an alteration of the baroreflex control of FVR was associated with the decreased blood pressure. Blood pressure, forearm blood flow (FBF), and estimated CVP were obtained in 13 hypertensive and 9 normotensive subjects evaluated in a randomized crossover fashion after 30 min of cycle ergometer exercise and after a nonexercise control period. In hypertensive subjects, the reduced blood pressure was accompanied by an increased baseline FBF after exercise. This resulted in a downward shift of the FVR-CVP relationship, while the slope was unchanged. In normotensive subjects, blood pressure and baroreflex control of FVR were unaffected by prior exercise. Four of the hypertensive subjects performed an additional study in which forearm skin was vasodilated with local heating to FVR levels similar to those observed after exercise. Results suggested that the aftereffects of exercise could not be attributed to changes in cutaneous blood flow. We speculate that modulation of the baroreflex control of FVR after exercise contributes to its antihypertensive effect.

Cold Temperature

Aftereffects of exercise on regional and systemic hemodynamics in hypertension.

Several studies have indicated that a single bout of physical exercise induced a significant antihypertensive effect during the hours after the activity. However, little information is presently available on the underlying hemodynamic changes. We examined 13 essential hypertensive patients and nine normotensive subjects in a randomized, crossover study design during 3 hours after a 30-minute period of upright leg cycling at 50% of peak aerobic capacity and during 3 hours after a 30-minute control period of rest. Blood pressure, heart rate, cardiac output, total peripheral resistance, and regional vascular resistance in the forearm as well as venous plasma catecholamine concentrations were measured repeatedly. After exercise, systolic (-11 +/- 2 mm Hg) and diastolic (-4 +/- 1 mm Hg) blood pressures, total peripheral resistance (-27 +/- 5%), forearm vascular resistance (-25 +/- 6%), and plasma norepinephrine levels (-21 +/- 7%) were significantly (p less than or equal to 0.05) decreased, and cardiac output was increased (+31 +1- 8%) compared with control in hypertensive subjects. In contrast, in normotensive subjects blood pressure, forearm vascular resistance, and plasma norepinephrine were unchanged, and systemic hemodynamics changed to a lesser extent than in hypertensive subjects after exercise. It is concluded that a decrease in regional vascular resistance in skeletal muscles and possibly in the skin in hypertensive patients may contribute importantly to the antihypertensive effect of prior exercise. A decreased sympathetic nervous activity, as seen from lower plasma norepinephrine levels, may be involved in this effect.

Adult

Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels.

The relations of regional adipose tissue (AT) distribution measured by computed tomography (CT) to plasma insulin-glucose homeostasis and lipoprotein-lipid levels were studied in 58 obese and 29 lean control men. In the group of obese men, the visceral AT area measured by CT was positively correlated with fasting plasma triglyceride and insulin levels and with glucose and insulin areas under the curves measured during a 75-g oral glucose tolerance test. Visceral AT area was also negatively associated with plasma high-density lipoprotein (HDL) and HDL2 cholesterol levels. The relative accumulation of abdominal fat, estimated by the ratio of abdominal to femoral AT areas obtained by CT, was also a significant correlate of indices of carbohydrate metabolism and was the best univariate correlate of plasma lipoprotein levels. No significant associations were observed between the visceral AT area, the ratio of abdominal to femoral AT areas, and indices of carbohydrate and lipoprotein metabolism in the group of lean men. On the other hand, the subcutaneous abdominal AT area was a significant correlate of the glucose area under the curve in both groups of men, but this association was not independent from the percentage of total body fat. No relationship was observed between the femoral AT area and indices of carbohydrate metabolism in either lean or obese groups. In obese men, however, the femoral AT area was negatively correlated with plasma triglyceride concentration and positively correlated with plasma HDL and HDL2 cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen

Adipose tissue lipolysis after long-term overfeeding in identical twins.

Ten pairs of young male sedentary, non-obese, monozygotic (MZ) twins, aged 21 +/- 2 years (mean +/- s.d.), were overfed for a period of 100 days during which they ingested 4.2 MJ (1000 kcal) per day above their individual energy needs, 6 days per week. There was a mean 8.4 kg increase in body weight and the average gain in body fat reaches 5.6 kg (P less than 0.0001). A biopsy of subcutaneous abdominal fat was performed, before and after the treatment, to determine fat cell weight as well as basal and catecholamine stimulated lipolyses from collagenase isolated adipocytes. Although analysis of variance revealed an increase in abdominal fat cell weight, no significant changes were noted in basal and catecholamine-stimulated lipolyses, due to large variation among individuals, results being expressed either per cell number or corrected for cell surface area. However, significant intrapair resemblance was observed in the changes of basal and epinephrine stimulated lipolyses (ri of about 0.60 in both cases), suggesting a concordant within-pair response, despite large between-pair variation. These results support the notion that the genotype may play an important role in regulating the response of abdominal adipose cells lipolytic activity to caloric excess.

Abdomen

Relation of abdominal obesity to hyperinsulinemia and high blood pressure in men.

The relationships between body fatness, adipose tissue distribution, plasma glucose, insulin levels, lipoprotein levels, and resting blood pressure were studied in 81 men aged 36.0 +/- 3.3 years (mean +/- s.d.) (body mass index (BMI): 27.4 +/- 3.8 kg/m2, percentage body fat: 26.4 +/- 6.6%). Systolic and diastolic blood pressures (BP) were significantly associated with the BMI (r = 0.31, r = 0.33, P < 0.01), the waist circumference (r = 0.33, r = 0.27; P < 0.01) as well as with adipose tissue areas measured by computerized tomography (CT) (0.27 < or = r < or = 0.36, P < 0.01). Furthermore, the relative accumulation of subcutaneous abdominal fat, as estimated by the ratio of abdominal to femoral adipose tissue areas measured by CT, was positively correlated with systolic and diastolic BP (P < 0.01). Fasting plasma insulin level (r = 0.30, P < 0.01) as well as the insulin area measured during an oral glucose tolerance test (0.34 < or = r < or = 0.37, P < 0.01) were significantly correlated with blood pressure. Systolic and diastolic BP were significantly associated with HDL2-cholesterol (C) as well as with the HDL2-C/HDL3-C ratio (-0.24 < or = r < or = -0.34), whereas triglycerides (r = 0.23) and the HDL-C/C ratio (r = -0.23) were significantly correlated with diastolic BP only (P < 0.05). Multivariate analysis indicated that the insulin area was the most important variable associated with blood pressure and that this association was independent of total body fatness and regional adipose tissue distribution. Plasma insulin levels explained 14% and 11% of the variance observed in the systolic and diastolic blood pressures respectively. These results suggest that most of the association between abdominal obesity and high blood pressure is mediated by the hyperinsulinemia and/or the related insulin resistant state.

Abdomen

Validation of the polyethylene glycol precipitation technique for the characterization of rat ventricular beta-adrenoceptors.

The use of polyethylene glycol (PEG) to separate [125I]cyanopindolol bound to rat ventricular membranes from free ligand in the characterization of beta-adrenoceptors was compared with the more frequently utilized filtration technique through GF/F glass-fiber filters. The results obtained in tissue from 14 rats demonstrated the following: (i) no significant difference between the two methods for the density of beta-adrenoceptors in ventricular tissue (PEG: 30.9 +/- 1.5 vs GF/F: 28.6 +/- 2.0 fmol/mg of protein); (ii) no significant difference for the dissociation constant (PEG: 70.7 +/- 5.3 vs GF/F: 57.7 +/- 7.7 pM); (iii) similar values for the Hill coefficient (PEG: 0.996 +/- 0.004 vs GF/F: 0.988 +/- .016); (iv) a significant difference for the relationship of bound/free vs bound, expressed as r2 (PEG: 0.82 +/- 0.03 vs GF/F: 0.74 +/- 0.03 P less than 0.05). The apparently greater accuracy of the PEG method over the filtration technique is probably explained by a lower degree of nonspecific binding observed with this method than with the filtration technique. In conclusion, the PEG precipitation method is an interesting and accurate alternative to the more standard filtration technique in ventricular beta-adrenoceptor characterization.

Animals

Effect of physical training on ventricular beta-adrenergic receptor adenylate cyclase system of diabetic rats.

This study was designed to assess the effect of physical training on the ventricular beta-adrenergic receptor adenylate cyclase system of diabetic rats. Mild diabetes mellitus was induced by an intravenous (IV) injection of streptozotocin (45 mg/kg). Rats were randomized into a group submitted to a progressive 10-week running program on a treadmill, while another group was kept sedentary. A group of sedentary nondiabetic rats was used as normal controls. Results showed a similar reduction in the density of beta-adrenergic receptors in sedentary diabetic (P less than .05) and trained diabetic rats (P less than .01) compared with controls, without any significant alteration in the dissociation constant. The basal and the sodium fluoride-stimulated maximal adenylate cyclase activities were similar in the three groups. However, the maximal response of adenylate cyclase to isoproterenol was significantly reduced in the two diabetic groups compared with controls (P less than .01). The decrease in adenylate cyclase response to isoproterenol observed in the diabetic groups appeared to be associated with a reduction in the total number of beta-adrenergic receptors and more specifically in those existing in the high-affinity state. On the other hand, the hyperglycemia and hyperglucagonemia present in sedentary diabetic rats was improved by training. These data suggest that the beneficial effects observed in response to training in experimental diabetes are not associated with changes in beta-adrenergic receptor adenylate cyclase system on membranes from ventricular tissue.

Adenylyl Cyclases

Thermogenic and hormonal responses to palatable protein and carbohydrate rich food.

Simultaneous variations of oxygen consumption, and plasma insulin and norepinephrine were measured during the postprandial cephalic and gastrointestinal phases of feeding in six human subjects following the ingestion of various nutrients. On alternative days the subjects were given foods (1280 kjoules) either rich in carbohydrates (sugar pie) or in proteins (fish). Both nutrients produced an initial (0-40 min) enhanced thermogenesis and an early (2 min) cephalic insulin release. During that period, elevations of plasma norepinephrine were also observed with pie feeding at 10 and 30 min and at 10 min with fish. Palatability ratings indicated that both food items were equally tasting. During the gastrointestinal phase (40 to 120 min) the variations of these same parameters including glucagon seem to be explained by the content in carbohydrates and proteins in the food rather than by its palatability. Indeed during that period the protein meal was more thermogenic and the carbohydrate meal induced the expected insulin secretion. These results suggest that the palatability of the food is responsible for the early cephalic increase in postprandial thermogenesis, and for the insulin and norepinephrine release. During the subsequent gastrointestinal phase the increased thermogenesis is related to the composition of the food which exerts its action by the biochemical processes involved in the disposal of the absorbed nutrients.

Adult

Human resting energy expenditure in relation to dietary potassium.

This study investigates the putative effect of potassium on energy expenditure. Eight young adult men were submitted to two different normocaloric mixed diets in a randomized order, containing either 163 +/- 9 or 69 +/- 2 mmol potassium/d. On the fifth day of each diet, after an overnight fast, resting metabolic rate (RMR) was measured over a 1-h period. After these measurements, either a potassium load (50 mmol) or a placebo were given to subjects submitted to the low- or the high-potassium diet, respectively. RMR was then measured again for 3 h and the last hour was kept for further analysis. Results showed that acute and chronic variations in potassium intake do not induce significant changes in RMR, and chronic but not acute changes in serum potassium concentration were significantly correlated with changes in energy expenditure (r = 0.74, P less than 0.05) by mechanisms that remain to be elucidated.

Adult