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Biomedical subjects

F X Pi-Sunyer

Publications and source records attributed to F X Pi-Sunyer.

At least 127 records · Page 7Linked to original sources

Lack of sustained increase in VO2 following exercise in fit and unfit subjects.

Thermogenesis after exercise was studied by measuring oxygen consumption in 23 subjects who were classified into three groups according to their routine level of physical activity. VO2 was first measured after a 30-minute rest period 4-hours after breakfast. Then each subject either exercised for 20 minutes at approximately the anaerobic threshold or on a separate non-exercise day remained recumbent. The subject then returned to, or remained, at rest. There was no significant difference in VO2 from the resting level from 40 minutes to 3 hours after exercise, between exercise and non-exercise days in any fitness group. Seven subjects also exercised for a longer period or at a higher intensity. Again, there was no significant difference in the time course of VO2 from 40 minutes to 220 minutes after exercise, between exercise and non-exercise days. Because no sustained effect of moderate or intense exercise on VO2 was demonstrated, we conclude that no appreciable caloric loss beyond that generated by the exercise period itself and the early recovery phase is found in either fit or unfit subjects. These data do not support claims for sustained increases in metabolic rate after exercise in weight-control programs.

Adult↗

The effects of inorganic chromium and brewer's yeast on glucose tolerance, plasma lipids, and plasma chromium in elderly subjects.

Twenty-three healthy, well-nourished, free-living elderly volunteers were given daily, for 10 wk, 5 g brewer's yeast, 200 micrograms Cr3+ as chromic chloride (CrCl3), or placebo. There were no significant changes in glucose tolerance, insulin, cholesterol or triglycerides after supplementation in any of the three groups. Plasma Cr3+ rose significantly after supplementation with CrCl3 but did not change after yeast or placebo supplementation. Plasma Cr3+ did not increase after an oral glucose load and did not correlate with glucose, insulin or lipid values in any of the groups. Calculated intakes of eight indicator nutrients were well above 100% of the RDA except for calcium. These healthy elderly persons, eating nutritious diets, are not at risk for Cr3+ deficiency as measured by the absence of a clinical response to CrCl3 or brewer's yeast supplementation. This study suggests that age per se is not a factor leading to Cr deficiency.

Aged↗

Effect of exercise on food intake in human subjects.

We review human studies of the effect of physical activity on food intake. Most are flawed by inaccurate measurement of energy expenditure and/or energy intake, by lack of controls, or by short study periods. While lean persons seem to regulate and maintain weight well, studies in obese subjects are inconclusive. At realistic exercise intensities, the effect on weight is generally small. There is little evidence of inhibition of food intake. In our metabolic ward studies, treadmill exercise neither enhanced nor inhibited food intake in obese individuals. Since intake remained fixed, a negative energy balance was observed with exercise. When more savory food was provided, intake again remained fixed as exercise was increased, but subjects ate more throughout and maintained positive energy balance. Thus, energy output does not regulate energy intake closely in the obese. Food-related cues seem more important than exercise-generated signals. The beneficial effect of exercise on body weight is limited to the extra calories expended. Further careful studies are essential to differentiate effects of kinds and intensities of exercise.

Body Weight↗

Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight.

The thermic effect of food at rest, during 30 min of cycle ergometer exercise, and after exercise was studied in eight lean (mean +/- SEM, 10 +/- 1% body fat, hydrostatically-determined) and eight obese men (30 +/- 2% body fat). The lean and obese mean were matched with respect to age, height, weight, and body mass index (BMI) to determine the relationship between thermogenesis and body composition, independent of body weight. All men were overweight, defined as a BMI between 26-34, but the obese had three times more body fat and significantly less lean body mass than the lean men. Metabolic rate was measured by indirect calorimetry under four conditions on separate mornings, in randomized order, after an overnight fast: 3 h of rest in the postabsorptive state; 3 h of rest after a 750-kcal mixed meal (14% protein, 31.5% fat, and 54.5% carbohydrate); during 30 min of cycling and for 3 h post exercise in the postabsorptive state; and during 30 min of cycling performed 30 min after the test meal and for 3 h post exercise. The thermic effect of food, which is the difference between postabsorptive and postprandial energy expenditure, was significantly higher for the lean than the obese men under the rest, post exercise, and exercise conditions: the increments in metabolic rate for the lean and obese men, respectively, were 48 +/- 7 vs. 28 +/- 4 kcal over 3 h rest (P less than 0.05); 44 +/- 7 vs. 16 +/- 5 kcal over 3 h post exercise (P less than 0.05); and 19 +/- 3 vs. 6 +/- 3 kcal over 30 min of exercise (P less than 0.05). The thermic effect of food was significantly negatively related to body fat content under the rest (r = -0.55), post exercise (r = -0.66), and exercise (r = -0.58) conditions. The results of this study indicate that for men of similar total body weight and BMI, body composition is a significant determinant of postprandial thermogenesis; the responses of obese are significantly blunted compared with those of lean men.

Adipose Tissue↗

Fatty acid mobilization to 2-deoxyglucose is blocked by globus pallidus lesions.

Lesions of the lateral hypothalamus or discrete bilateral transections on the lateral border of the lateral hypothalamus disrupt the mobilization of metabolic fuels to intraperitoneal administration of the glucose analog 2-deoxyglucose. To better define the pathways involved in these responses, the effects of globus pallidus lesions on body fuel mobilization were investigated. Globus pallidus lesions blocked the increase in plasma free fatty acids normally caused by 2-deoxyglucose, but did not diminish the concomitant hyperglycemia. The data indicate that a pathway running through the globus pallidus, crossing the dorsoanterolateral hypothalamic border, and turning caudally in the dorsolateral hypothalamus is important in the immediate release of free fatty acids following 2-deoxyglucose administration.

Animals↗

Influence of sympathectomy on the lateral hypothalamic lesion syndrome.

Sympathetic involvement in the lateral hypothalamic (LH) lesion syndrome was examined. Male rats were surgically or chemically sympathectomized and then given LH lesions. At 24 hr postlesion, lesion-induced hyperglycemia but not hyperthermia was attenuated by splanchnicectomy and celiac ganglionectomy. Hyperthermia but not hyperglycemia was attenuated by adrenal demedullation, adrenalectomy, and neonatal guanethidine treatment. Guanethidine-sympathectomized rats also displayed lower basal temperatures, more perilesion chromatolysis, and severer external symptoms than their controls. No form of sympathectomy affected lesion-induced gastric pathology, plasma gastrin concentrations, or body weight loss. Nor did any sympathectomy influence the recovery of ingestive behavior, daily food intake, the feeding response to 2-deoxy-D-glucose, or body weight maintenance in recovered LH-lesion subjects. These results suggest that sympathetic hyperactivity contributes to some aspects of the acute LH syndrome: Hyperglycemia results from sympathetic outflow to the abdomen, whereas hyperthermia is determined by circulating catecholamines and extraabdominal sympathetic innervation. The results fail to support the hypothesis that chronic increases in sympathetic tone are responsible for the reduced food intake and body weight of the LH-lesion rat.

Animals↗

Elevated postprandial insulin levels do not induce satiety in normal-weight humans.

To determine whether an elevated insulin level contributes to satiety, two experiments were conducted using a covert system of monitoring food intake. Normal-weight volunteers received intravenous infusion of either 0.15 M saline or a mixture of glucose and insulin during a single-course meal. In the first group, the glucose-insulin infusion (0.03 U insulin X kg-1 X h-1 and 0.25 g glucose X kg-1 X h-1) was begun 30 min before the start of the test meal and ended 15 min after subjects had voluntarily stopped eating. Plasma insulin was raised threefold, and glucose increased 20 mg/dl above preinfusion base line at time of eating. In the second group, the glucose-insulin mixture (insulin bolus of 12 mU/kg plus 0.03 U insulin X kg-1 X h-1 and 0.125 g glucose X kg-1 X h-1) was delivered 12 min after an appetizer was served and just as the test meal began. This infusion was stopped 12 min after the end of the meal. Serum insulin was fourfold higher than saline infusion levels at onset of eating, but glucose remained the same. The changes induced in these studies by the glucose-insulin infusions mimicked normal insulin and glucose levels seen shortly before satiation is complete in a meal. No effect on meal size or duration was observed. Therefore normal postprandial elevation of insulin is unlikely to signal satiety in humans.

Eating↗

Murine islet cryopreservation and corticosteroids: functional studies.

Knowledge of protective effects of corticosteroids on traumatized cells prompted us to test the potential benefit of islet cryopreservation in the presence of hydrocortisone. Neonatal murine islets were isolated by collagenase, followed by 2- to 3-day tissue culture. Precryopreservation glucose-stimulated (50-500 mg/dl) insulin release was 25-388% above basal (mean = 113%) in 18/20 fresh islet preparations. Subsequent freezing was done in RPMI 1640 medium plus 10% (v/v) heat-inactivated fetal calf serum and 10% (v/v) Me2SO with or without 1 mg/ml hydrocortisone at 0.25 degrees C per minute in a programmed freezing system, to -80 degrees C, and stored for greater than 60 days at -196 degrees C. Thawing, by transfer to room air, was followed by dilution, 4x (v/v), in 4 degrees C RPMI plus 10% protein, after which glucose-stimulated insulin release was reassessed, showing 56-280% response over basal in 3/8 steroid-treated preparation and 20-220% response in 3/10 control preparations. Basal insulin release was 0.72 ng/microgram protein/hr in fresh islets (N = 20) and 0.22 ng/microgram protein/hr after freeze-thawing. We conclude that functional islet survival by this method is approximately 30% and that hydrocortisone did not improve viability.

Adrenal Cortex Hormones↗

Prediction of the resting metabolic rate in obese patients.

Resting metabolic rate (RMR) was measured in 154 women and 48 men before the beginning of a weight reduction program. In both sexes there were significant univariate correlations between RMR and fat-free mass, body fat, weight, fat cell weight, and fat cell number (from total body water). Women also showed significant correlations between RMR and fat cell number (from total body potassium), free triiodothyronine index, and fasting and postglucose insulin levels. Multiple regression analysis showed that both fat-free mass and fat cell weight and number were significant predictors of RMR. The contribution of fat-free mass was three to five times greater per kg than that of body fat. There was no significant contribution of thyroid hormones or insulin to the prediction of RMR. Fat cell number and fat cell weight were significant predictors of RMR, whether determined from body water, body potassium, or a formula using both water and potassium. There was no significant difference in regression coefficients between men and women. Thus the difference in RMR between the sexes is probably caused by the higher proportion of fat-free mass in men. The effect of age was small and not statistically significant.

Adipose Tissue↗

Variations of glucose metabolism by fat cells from three adipose depots of the rat.

Fat cells isolated from the epididymal (E) and dorsal subcutaneous (S) depots from 150g male Wistar rats were similar in size, but differed markedly in glucose metabolism. Retroperitoneal (RP) fat cells were slightly larger but were metabolically similar to epididymal fat cells. Basal incorporation of [1-14C] glucose into fatty acids was lower in S than E and RP, CO2 production and glyceride-glycerol synthesis were similar in all three; and lactate production was increased in RP and S compared to E. S adipocytes exhibited a blunted respond to both submaximally and maximally-stimulating concentrations of insulin compared to RP and E adipocytes in glucose incorporation into fatty acids, CO2 and lactate production, but not glyceride-glycerol. Maximally insulin-stimulated fatty acid synthesis by S fat cells was 19% and 29% of the values in E and RP fat cells respectively. Basal and maximally insulin-stimulated glucose transport (2-deoxy [14C] glucose uptake) was depressed by 30%-40% in S cells compared to E and RP. Thus, the decreased basal glucose utilization of S could be attributed primarily to a decreased glucose transport capacity. The markedly lower insulin-stimulated glucose metabolism in S fat cells, however, may be explained by alterations of the capacities for both transport and intracellular metabolism. Subcutaneous fat cells were also somewhat less sensitive to submaximal doses of insulin and this was reflected in rightward shift in the dose-response curves for 2-deoxyglucose uptake and fatty acid synthesis. The decreases in insulin stimulated glucose oxidation and fatty acid synthesis were paralleled by decreases in the major lipogenic enzymes. Although the reason for these variations in the capacity for glucose metabolism among depots is unknown, they are important in assessing the metabolic function of the whole adipose organ.

Adipose Tissue↗

Effect of exercise on spontaneous calorie intake in obesity.

The effect of increased physical activity on energy intake and balance was investigated in six obese women (mean 167% above ideal body weight) voluntarily hospitalized for metabolic balance studies. Three 19-day treatments-one sedentary and two with treadmill exercise which increased daily expenditure to 110% (mild) and 125% (moderate) of sedentary expenditure-were imposed on each subject. Individual daily expenditure and ad libitum intake were determined by activity diaries and covert monitoring, respectively. Subjects selected and did not not change an intake level which allowed for energy balance during the sedentary period only. Therefore, the difference between intake and expenditure between treatments was significantly different (sedentary 11, mild -114, and moderate -369 kcal/day). The negative balance observed with mild and moderate exercise was obtained because while expenditure was raised with exercise, no compensatory increase in intake occurred. Moderate, realistic levels of activity did not regulate intake.

Adult↗

Voluntary food intake during prolonged exercise in obese women.

The effect of 57 days of moderate physical activity on the energy intake and balance of three obese women (187% of ideal weight) was investigated in a metabolic balance study. Food was offered in extra quantity, prepared in a palatable but simple fashion, and intake was covertly monitored. Expenditure was measured using the factorial method and indirect calorimetry done every 3 to 4 days. After a 5-day evaluation phase which no exercise was done, individual treadmill assignments were given to subjects to increase daily expenditure to 125% of sedentary levels. Mean dialy intake (1903 kcal/day) and expenditure (2882 kcal/day) did not change with time. As a result, negative energy balance was obtained and sustained. A consistent rate of weight loss (0.12 kg/day) at a reasonable cost (8200 kcal/kg)occurred. Therefore, obese women doing long-term moderate exercise do not compensate by an increase in caloric intake. This can produce a negative caloric balance when exercise is coupled with ad libitum selection of ordinary foods.

Adolescent↗

Altered insulin and glucagon secretion in perfused ethionine-treated rat pancreases.

The endocrine secretory function of rat pancreases in which pancreatitis had been induced by feeding rats a 0.5% ethionine diet was investigated. Despite loss of 50% of exocrine tissue and widespread destruction of acinar structure, pancreatic insulin and glucagon contents and 4-h fasting plasma insulin levels in vivo did not differ significantly from those of food-restricted, weight-matched controls. Plasma glucose concentrations (fasting and after oral glucose) were significantly lower than control. In isolated, perfused ethionine-treated pancreases secretin failed to stimulate insulin secretion, whereas basal insulin secretion and insulin responses to glucose, arginine, gastric inhibitory polypeptide, vasoactive intestinal peptide (VIP), and somatostatin were similar to those of controls. Basal glucagon secretion was elevated in ethionine-treated pancreases, and glucagon outputs in response to arginine, VIP, and somatostatin showed a consistent trend toward higher levels than those of controls. These findings demonstrate that ethionine-induced pancreatitis selectively impairs islet secretory function. These effects may be due to damage to islet cell membranes by exocrine enzymes and/or a direct pathogenic action of ethionine on the islets.

Animals↗

Normal responses of rats with transplanted neonatal islets to stress, epinephrine, and cortisol.

Sympathetic responses were evaluated in rats transplanted with neonatal pancreatic tissue. Transplantation was by one of two methods: mild collagenase digestion with subsequent intraportal injection, or direct placement of intact pancreatic tissue under the renal capsule. Compared with control intact animals, both groups of transplanted rats reverted to normal fasting and postglucose load plasma glucose and insulin. The hyperglycemia characteristic of stress or of injected exogenous epinephrine was present and similar in all three groups. The response to an intragastric glucose load or to tolbutamide injection during stress was similar in transplanted and in control animals. All three groups of rats responded to sustained cortisol injection with a compensatory hyperinsulinemia but maintained normal plasma glucose, water intake, and urine volume. No evidence could be detected in this study of an exaggerated "denervated" response of the transplanted islets. The normal sympathetic responses of these neonatal islet preparations in which little or no collagenase was used, in comparison with the abnormal responses previously reported for collagenase-treated individually isolated adult rat islets, suggest differences in recuperative powers of the sympathetic innervation in islets, possibly related to age and to method of preparation of transplanted tissue.

Animals↗