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Biomedical subjects

F Zurlo

Publications and source records attributed to F Zurlo.

At least 19 recordsLinked to original sources

Whole-body energy metabolism and skeletal muscle biochemical characteristics.

A low metabolic rate for a given body size and a low fat versus carbohydrate oxidation ratio are known risk factors for body weight gain, but the underlying biological mechanisms are poorly understood. Twenty-four-hour energy expenditure (24EE), sleeping metabolic rate (SMR), 24-hour respiratory quotient (24RQ), and forearm oxygen uptake were compared with respect to the proportion of skeletal muscle fiber types and the enzyme activities of the vastus lateralis in 14 subjects (seven men and seven women aged 30 +/- 6 years [mean +/- SD], 79.1 +/- 17.3 kg, 22% +/- 7% body fat). The following enzymes were chosen to represent the major energy-generating pathways: lactate dehydrogenase (LDH) and phosphofructokinase (PFK) for glycolysis; citrate synthase (CS) and beta-hydroxyacl-coenzyme A dehydrogenase (beta-OAC) for oxidation; and creatine kinase (CK) and adenylokinase (AK) for high-energy phosphate metabolism. Forearm resting oxygen uptake adjusted for muscle size correlated positively with the proportion of fast-twitch muscle fibers (IIa: r = .55, P = .04; IIb: r = .51, P = .06) and inversely with the proportion of slow oxidative fibers (I: r = -.77, P = .001). 24EE and SMR adjusted for differences in fat-free mass, fat mass, sex, and age correlated with PFK activity (r = .56, P = .04 and r = .69, P = .007, respectively). 24RQ correlated negatively with beta-OAC activity (r = -.75, P = .002). Our findings suggest that differences in muscle biochemistry account for part of the interindividual variability in muscle oxygen uptake and whole-body energy metabolism, ie, metabolic rate and substrate oxidation.

Adult↗

Body composition study in the elderly: comparison between tritium dilution method and dual photon absorptiometry.

BACKGROUND: The methods commonly employed in body composition study in elderly persons derive fat-free mass (FFM) by measures of total body water (TBW); these methods assume FFM hydration constant (TBW/FFM = 0.732). The aim of our study was to verify the accuracy of the TBW method in FFM estimation and to study the variability of fat-free mass hydration (TBW/FFM) in healthy elderly subjects. METHODS: We assessed FFM in 27 healthy old subjects (76 +/- 7 yrs) by dual photon absorptiometry (DPA) and by TBW measured by 3H2O. Furthermore, to verify the accuracy in FFM estimation by our methods, we measured resting metabolic rate (RMR) by indirect calorimetry. RESULTS: FFM hydration was 71.9 +/- 4.9 (range 63.6-80.4%), a range larger than that reported by direct chemical analysis in adults. The FFM hydration measured in our subjects was not different from the 73.2 value currently used in healthy adults. FFM values derived by TBW (assuming TBW/FFM = 0.732) were not significantly different from FFM measured by DPA. We correlated FFM with resting metabolic rate and found a similar correlation between RMR and FFM-DPA (r = .89, p < .001) and FFM-TBW (r = .85, p < .001). CONCLUSIONS: Both methods employed in our study have proved to be accurate in estimating FFM in elderly persons; particularly, the value of 0.732 assigned to FFM hydration to derive fat-free mass in adults can be employed also in body composition study of the elderly.

Absorptiometry, Photon↗

Spontaneous physical activity and obesity: cross-sectional and longitudinal studies in Pima Indians.

Healthy, nondiabetic Pima Indians [103 males, 77 females; 27 +/- 6 (SD) yr, 97 +/- 25 kg, 33 +/- 9% body fat] were studied in a respiratory chamber in which spontaneous physical activity (SPA) was measured by two microwave sensors. SPA, defined as the percentage of time the subjects were active, varied widely from 4.4 to 17.5%. It was higher in males (9.3 +/- 2.0%) than in females (8.6 +/- 2.3%; P less than 0.05) and was not related to body fatness in either sex. However, SPA accounted for a significant portion of the daily energy expenditure (24-h EE) in males (1,389 +/- 423 kJ/day) and females (1,163 +/- 351 kJ/day) and correlated positively with 24-h EE adjusted for differences in fat-free mass, fat mass, age, and sex (r = 0.42, P less than 0.0001). In 88 siblings, family membership accounted for 57% of the variance in SPA (r(i) = 0.57, P less than 0.02). Body composition was reassessed in a subgroup of 123 subjects (65 males, 58 females) 33 +/- 14 mo later. In males only, SPA correlated inversely to the rate of subsequent body weight change (r = -0.25, P less than 0.05) and the rate of fat-mass change (r = -0.35, P less than 0.005). We conclude that spontaneous physical activity is a familial trait that may play a role in the pathogenesis of obesity.

Adult↗

Assessment of abdominal fat distribution in obese patients: anthropometry versus computerized tomography.

The accuracy of waist to hip girth ratio (WHR) in assessing visceral/subcutaneous abdominal fat distribution has not yet been clearly established in the obese population. The purpose of the present study was to evaluate the relationship between WHR and visceral/subcutaneous fat distribution, both assessed by computerized tomography (CT), in a group of 28 obese patients (15 male, 13 female). Furthermore, 33 normal weight or slightly overweight subjects (23 male, 10 female) were studied as a control group. Obese subjects of both sexes were found to have higher values of WHR than non-obese; conversely visceral:subcutaneous fat area ratio (VSR) values did not differ significantly. Significant correlation between WHR and BMI was present both in males (r = 0.41, P < 0.01) and in females (r = 0.54, P < 0.01). In normal weight males significant correlations between WHR and visceral fat area or VSR were found. In obese males these correlations were much weaker. In normal weight females a significant correlation was found between waist circumference and visceral fat area, whereas in obese females no positive correlations were found between anthropometric measurements and CT indices of visceral fat distribution. In conclusion, WHR cannot be considered as a reliable index of visceral/subcutaneous fat distribution in obese patients, particularly if they are females.

Abdomen↗

Aging and energy expenditure.

Whether sedentary energy expenditure is normal or lower in elderly people has not yet been clearly established. Twenty-four-hour energy expenditure (24EE) and its different components were measured by use of a respiratory chamber in elderly (17 male, 21 female; 71 +/- 6 y, mean +/- SD; 71.2 +/- 13.5 kg; 32 +/- 8% fat) and young (33 male, 31 female; 24 +/- 4 y; 84.5 +/- 23.1 kg; 25 +/- 13% fat) subjects. The elderly subjects had lower mean height (P less than 0.001), weight (P less than 0.01), and fat-free mass (P less than 0.001) but higher percent body fat (P less than 0.01) than did the young adults. Absolute 24EE, basal metabolic rate (BMR), and sleeping metabolic rate were significantly lower (P less than 0.01) in the elderly subjects than in the young subjects. However, after differences in fat-free mass, fat mass, and sex were adjusted for, only BMR was found to be lower in the elderly subjects (P less than 0.01). Despite a reduced adjusted BMR in older subjects, sedentary 24EE was decreased only in proportion to their reduced body size, suggesting that the lower energy intake reported in elderly people might be mainly related to lower physical activity in free-living conditions.

Adipose Tissue↗

Muscle mitochondrial morphology, body composition, and energy expenditure in sedentary individuals.

To investigate whether differences in metabolic rate are related to differences in muscle mitochondrial morphology and/or to differences in in vitro muscle respiration, we studied 17 healthy Caucasians, covering a wide range of body weight and composition [9 males, 8 females; body wt 96 +/- 37 (SD) kg; body fat = 28 +/- 10%]. Central and peripheral mitochondrial volume density (Vmit c and Vmit p, respectively) and the ratio of mitochondrial outer surface to volume of mitochondria (SVmit c in center and SVmit p at periphery) were determined by stereological analyses of transmission electron micrographs from samples of the vastus lateralis. There was no relationship between mitochondrial morphology or muscle respiration and 24-h energy expenditure, basal metabolic rate, or sleeping energy expenditure adjusted for differences in fat-free mass, fat mass, age, and sex. Although total body fat was not associated with muscle cell morphology, central distribution of body fat [waist-to-thigh circumference ratio (W/T)] correlated negatively with Vmit c (r = -0.58, P = 0.01), SVmit c (r = -0.59, P = 0.01), and SVmit p (r = -0.48, P = 0.05). W/T was also negatively related to muscle respiration (r = -0.59, P = 0.01). Despite the lack of relationship between metabolic rate and muscle mitochondrial morphology, central distribution of body fat is associated with lower mitochondrial density and larger mitochondria in skeletal muscle and is associated with a decreased oxidative capacity of muscle.

Adult↗

Ethnic differences in sympathetic nervous system-mediated energy expenditure.

The impact of sympathetic nervous system (SNS) activity on energy expenditure (EE) was evaluated in nondiabetic Caucasian and Pima Indian men while on a weight-maintenance diet using two approaches as follows. 1) The relationship between 24-h EE, measured in a respiratory chamber, and 24-h urinary norepinephrine was studied in 36 Caucasians [32 +/- 8 (SD) yr, 95 +/- 41 kg, 22 +/- 13% fat] and 33 Pimas (29 +/- 6 yr, 103 +/- 28 kg, 30 +/- 9% fat). There was no difference between the two groups in 24-h EE (2,422 vs. 2,523 kcal/24 h) and in urinary norepinephrine (28 vs. 31 micrograms/24 h), even after adjusting for body size and composition. Twenty-four-hour EE correlated significantly with 24-h urinary norepinephrine in Caucasians (r = 0.78, P less than 0.001) but not in Pimas (r = 0.03), independent of fat-free mass (FFM), fat mass, and age. 2) The effect of beta-adrenoceptor blockade with propranolol (120 micrograms/kg FFM bolus and 1.2 micrograms.kg FFM-1.min-1 for 45 min) on the resting metabolic rate (RMR) was evaluated in 36 Caucasians (30 +/- 6 yr, 103 +/- 36 kg, 25 +/- 11% fat) and 32 Pimas (28 +/- 6 yr, 100 +/- 34 kg, 27 +/- 10% fat). The RMR was similar in the two groups (2,052 vs. 1,973 kcal/24 h) even after adjustment for FFM, fat mass, and age and dropped significantly after propranolol infusion in Caucasians (-3.9%, P less than 0.001) but not in Pimas (-0.8%, P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Activation of skeletal muscle casein kinase II by insulin is not diminished in subjects with insulin resistance.

Insulin resistance, which may precede the development of non-insulin-dependent diabetes mellitus in Pima Indians, appears to result from a postreceptor defect in signal transduction in skeletal muscle. To identify the putative postreceptor lesion responsible for insulin resistance in Pima Indians, we investigated the influence of insulin on the activity of casein kinase II (CKII) in skeletal muscle of seven insulin-sensitive, four insulin-resistant, nondiabetic, and five insulin-resistant diabetic Pima Indians during a 2 h hyperinsulinemic, euglycemic clamp. In sensitive subjects, CKII was transiently activated reaching a maximum over basal activity (42%) at 45 min before declining. CKII was also stimulated in resistant (19%) and diabetic (34%) subjects. Basal CKII activity in resistant subjects was 40% higher than in either sensitive or diabetic subjects, although the concentration of CKII protein, as determined by Western blotting, was equal among the three groups. Basal CKII activity was correlated with fasting plasma insulin concentrations, suggesting that the higher activity in resistant subjects resulted from insulin action. Extracts of muscle obtained from all three groups either before or after insulin administration were treated with immobilized alkaline phosphatase, which reduced and equalized CKII activity. These results suggest that insulin stimulates CKII activity in human skeletal muscle by a mechanism involving phosphorylation of either CKII or of an effector molecule, and support the idea that elevated basal activity in resistant subjects results from insulin action. It appears that the ability of insulin to activate CKII in skeletal muscle is not impaired in insulin-resistant Pima Indians, and that the biochemical lesion responsible for insulin resistance occurs either downstream from CKII or in a different pathway of insulin action.

Alkaline Phosphatase↗

Insulin resistance associated with lower rates of weight gain in Pima Indians.

UNLABELLED: Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change is unknown. We measured glucose disposal rates at submaximally- and maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians and followed their weight change over 3.5 +/- 1.8 y (mean +/- SD). RESULTS: (a) Insulin-resistant subjects gained less weight than insulin-sensitive subjects (3.1 vs. 7.6 kg, P less than 0.0001). (b) The percent weight change per year correlated with glucose disposal at submaximally-(r = 0.19, P less than 0.01) and maximally-stimulating (r = 0.34, P less than 0.0001) insulin concentrations independent of sex, age, initial weight, and 24-h energy expenditure; the correlations were stronger for glucose oxidation than for glucose storage. (c) Weight gain was associated with an increase in insulin resistance more than four times that predicted from the cross-sectional data. We conclude that insulin resistance is associated with a reduced risk of weight gain in nondiabetic Pima Indians.

Adolescent↗

Insulin regulation of glucose and lipid metabolism in massive obesity.

Eight obese patients and 12 normal individuals underwent a euglycaemic insulin clamp (20 and 40 mU m2-1.min-1) along with continuous infusion of 3-3H-glucose and 1-14C-palmitate and indirect calorimetry. Basal plasma glucose concentration (4.7 +/- 0.3 vs 4.4 +/- 0.2 mmol/l) was similar in the two groups, whereas hepatic glucose production was slightly higher in obese individuals (1.11 +/- 0.06 vs 0.84 +/- 0.05 mmol/min) in spite of higher plasma insulin levels (17 +/- 2 vs 6 +/- 1 mU/l; p less than 0.01). Insulin inhibition of hepatic glucose production was impaired in obese subjects. Glucose disposal by lean body mass was markedly reduced both at baseline (11.7 +/- 1.1 vs 15.6 +/- 0.6 mumol.kg-1.min-1; p less than 0.05) and during clamp (15.0 +/- 1.1 vs 34.4 +/- 2.8 and 26.7 +/- 3.9 vs 62.2 +/- 2.8 mumol.kg-1.min-1; p less than 0.01) Oxidative (12.2 +/- 1.1 vs 17.8 +/- 1 and 16.1 +/- 1.1 vs 51.1 +/- 1.7 mumol.kg-1.min-1; p less than 0.05-0.002) and non-oxidative glucose metabolism (3.9 +/- 1.1 vs 15.0 +/- 2.8 and 12.8 +/- 3.3 vs 38.2 +/- 2.2 mumol.kg-1.min-1; p less than 0.01-0.001) were impaired. Basal plasma concentrations of non-esterified fatty acids (635 +/- 75 vs 510 +/- 71 mumol/l) and blood glycerol (129 +/- 17 vs 56 +/- 5 mumol/l; p less than 0.01) were increased in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metabolic and hormonal effects of early nutritional supplementation after surgery in burn patients.

We evaluated, in burn patients, the metabolic and hormonal effects of early nutritional supplementation after a severe stress event represented by the deep surgical excision of the burn wounds and autograft coverage. The surgical procedure induced a 50% increase from baseline value of the resting metabolic rate. Immediate nutritional supplementation avoids the adaptive stress-related increments of urinary catecholamine excretion and glucagon secretion while insulin secretion is maintained. The urinary cortisol excretion, significantly increased after surgery in study and control groups, was unaffected by the nutritional intervention. The favorable insulin/glucagon ratio and the control of catecholamine response in early nutritionally supplemented patients are associated with the maintenance of a positive N balance in the days after surgery.

Adult↗

Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ.

Reduced oxidation of fat leading to a positive fat balance could be a factor in the development of obesity. Twenty-four-hour respiratory quotient (RQ) was measured in 152 nondiabetic Pima Indians fed a weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean +/- SD); 93.9 +/- 22.9 kg; 32 +/- 9% fat]. Twenty-four-hour RQ varied from 0.799 to 0.903. Prior change in body weight, 24-h energy balance, sex, and percent body fat explained 18% of the variance in 24-h RQ (P less than 0.001). In a subgroup of 66 siblings from 28 families, family membership explained 28% of the remaining variance in 24-h RQ (P less than 0.05). In 111 subjects for whom follow-up data (25 +/- 11 mo) were available, 24-h RQ was correlated with subsequent changes in body weight and fat mass (r = 0.27, P less than 0.01 and r = 0.19, P less than 0.05, respectively). Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile). We conclude that in Pima Indians fed a standard diet 1) family membership is the principal determinant of the ratio of fat to carbohydrate oxidation, and 2) a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity.

Adult↗

Skeletal muscle metabolism is a major determinant of resting energy expenditure.

Energy expenditure varies among people, independent of body size and composition, and persons with a "low" metabolic rate seem to be at higher risk of gaining weight. To assess the importance of skeletal muscle metabolism as a determinant of metabolic rate, 24-h energy expenditure, basal metabolic rate (BMR), and sleeping metabolic rate (SMR) were measured by indirect calorimetry in 14 subjects (7 males, 7 females; 30 +/- 6 yr [mean +/- SD]; 79.1 +/- 17.3 kg; 22 +/- 7% body fat), and compared to forearm oxygen uptake. Values of energy expenditure were adjusted for individual differences in fat-free mass, fat mass, age, and sex. Adjusted BMR and SMR, expressed as deviations from predicted values, correlated with forearm resting oxygen uptake (ml O2/liter forearm) (r = 0.72, P less than 0.005 and r = 0.53, P = 0.05, respectively). These findings suggest that differences in resting muscle metabolism account for part of the variance in metabolic rate among individuals and may play a role in the pathogenesis of obesity.

Adult↗

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

Adult↗

Distribution of in vivo insulin action in Pima Indians as mixture of three normal distributions.

If a single gene produced insulin resistance, with environmental effects creating some additional variance, insulin action might be distributed as a mixture of two normal distributions if the gene is dominant or recessive or as a mixture of three normal distributions if the gene is codominant. To estimate maximal insulin-stimulated glucose uptake rates (MaxMs), hyperinsulinemic-euglycemic clamps were performed on 245 nondiabetic Pima Indians (126 men, 119 women). Five models (for 1, 2, 3, 4, or 5 components each, normally distributed with a common variance) were fitted to the frequency distribution of MaxM by iterative maximum-likelihood estimation. The three-component model fit the data significantly better than a single normal distribution (chi 2 = 14.3 with 4 df P less than .01) or a mixture of two normal distributions (chi 2 = 9.9 with 2 df, P less than .01). Mixtures of four or five normal distributions did not fit the data significantly better than a mixture of three normal distributions. The first component of the distribution comprised 23%, the second 48%, and the third 29% of the total distribution. Similarly, the frequency distributions of fasting plasma insulin concentrations and a principal component score derived from MaxM and fasting insulin were best fitted by a mixture of three normal distributions. These results are consistent with the hypothesis that among Pimas, insulin resistance is determined by a single gene with a codominant mode of inheritance. Segregation analyses of studies performed in pedigrees are indicated to prove or disprove this genetic hypothesis.

Adult↗

[Effect of L-carnitine supplemented total parenteral nutrition on postoperative lipid and nitrogen utilization].

During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were equally and randomly divided and received isonitrogenous (0.2 gN/kg.day) and isocaloric (35 kcal/kg.day TPN over 11 days without and with L-carnitine supplementation (12 mg/kg.day). Compared with healthy controls, the total body carnitine pool was significantly reduced in both groups prior to the operation. Without supplementation carnitine concentrations were maintained, while daily provision of carnitine resulted in an elevation of total carnitine mainly due to an increase of the free fraction. Without supplementation the cumulative urinary carnitine losses were 11.5 +/- 6.3 mmol corresponding to 15.5% +/- 8.5% of the estimated total body carnitine pool. Patients receiving carnitine revealed a positive carnitine balance in the immediate postoperative phase, 11.1% +/- 19.0% of the infused carnitine being retained. After 11 days of treatment comparable values for respiratory quotient, plasma triglycerides, free fatty acids, ketone bodies, and cumulative nitrogen balance were observed. It is concluded that in the patient population studied here carnitine supplementation during postoperative TPN did not improve fat oxidation or nitrogen balance.

Adult↗

Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians.

Impaired glucose tolerance often presages the development of non-insulin-dependent diabetes mellitus. We have studied insulin action and secretion in 24 Pima Indians before and after the development of impaired glucose tolerance and in 254 other subjects representing the whole spectrum of glucose tolerance, including subjects with overt non-insulin-dependent diabetes. The transition from normal to impaired glucose tolerance was associated with a decrease in glucose uptake during hyperinsulinemia, from 0.018 to 0.016 mmol per minute (from 3.3 to 2.8 mg per kilogram of fat-free body mass per minute) (P less than 0.0003). Mean plasma insulin concentrations increased during an oral glucose-tolerance test, from 1200 to 1770 pmol per liter (from 167 to 247 microU per milliliter). In 151 subjects with normal glucose tolerance, the insulin concentration measured during an oral glucose-tolerance test correlated with the plasma glucose concentration (r = 0.48, P less than or equal to 0.0001). This relation was used to predict an insulin concentration of 1550 pmol per liter (216 microU per milliliter) in subjects with impaired glucose tolerance (actual value, 1590 pmol per liter [222 microU per milliliter]; P not significant), suggesting that these subjects had normal secretion of insulin. In contrast, plasma insulin concentrations in the diabetics decreased as glucose concentrations increased (r = -0.75, P less than or equal to 0.0001), suggesting deficient secretion of insulin. This relative insulin deficiency first appears at the lower end of the second (diabetic) mode seen in population frequency distributions of plasma glucose concentrations. Our data show that impaired glucose tolerance in our study population is primarily due to impaired insulin action. In patients with non-insulin-dependent diabetes mellitus, by contrast, impaired insulin action and insulin secretory failure are both present.

Adult↗

Lipid metabolism in lipoatrophic diabetes.

Some aspects of lipid metabolism were studied in 4 patients with a congenital lipoatrophic diabetes (LAD) associated to a type IV hyperlipoproteinemia. The analysis of lipoprotein composition, expressed as mg/dl, demonstrates a significant increase of VLDL mass and a significant reduction of HDL mass. The analysis of lipoprotein composition, expressed as per cent of total mass demonstrates an increase of the triglyceride content in all fractions and a significant reduction of the cholesterol and phospholipid content in HDL2 particles. Apo C-II, C-III0, C-III1 and C-III2 levels in lipoprotein fractions were normal in LAD patients. Lipoprotein lipase activity in omental adipose tissue, collected during laparoscopy in one patient was undetectable. The serum of this patient did not fully activate the lipoprotein lipase eluted from normal adipose tissue. In all patients the adipose tissue lipoprotein lipase activity in post-heparin plasma was blunted or near absent. Thus a reduced peripheral clearance of triglyceride-rich lipoprotein could be an important determinant of lipoprotein abnormalities in lipoatrophic diabetes.

Adipose Tissue↗