Development and validation of the Symptomatic Transdiagnostic Test (S2T).

INTRODUCTION: The categorical approach in psychiatry has received many criticisms. Modern research tends to develop a transdiagnostic approach. However, transdiagnostic works lack an overall understanding and focus mainly on anxiety and depression. The aim of the present study was to develop an easy to use tool to evaluate multiple dimensions opening the way for further research in the transdiagnostic approach. This will allow researchers to quickly assess the efficacy of psychotherapeutic interventions on multiple psychopathological dimensions. METHOD: First, we identified the main symptoms of psychopathology in a sample of mental healthcare workers. Second, we developed the Symptomatic Transdiagnostic Test (S2T) to assess the main symptoms of psychopathology. Third, we evaluated its psychometric properties (exploratory and confirmatory factor analysis, internal consistency) in three non-clinical samples and one clinical sample. RESULTS: The 66-item S2T included eleven factors referring to: i) negative thoughts and mood; ii) psycho-traumatic and maladaptive symptoms; iii) addiction symptoms; iv) disturbed eating behavior; v) disturbed perception and behavior; vi) panic and agoraphobia; vii) emotional lability; viii) dejection; ix) neurodevelopmental manifestations; x) anxiety and xi) psychic hyperactivity. We found a high internal consistency for the general scale (α=0.96) and the subscales. We found a good concurrent validity. As expected, we found higher levels of symptoms within the clinical population as compared to the non-clinical samples, except for addiction symptoms and disrupted eating behavior. We found negative associations between the symptomatic dimensions and psychological skills. CONCLUSION: The S2T is a relevant tool for clinicians and researchers to assess the psychopathological profile. The main psychopathological symptoms are negatively related to the psychological skills.

Changes in body composition during weight loss in obese subjects in the NUGENOB study: comparison of bioelectrical impedance vs. dual-energy X-ray absorptiometry.

AIM: We studied the accuracy of bioelectrical impedance analysis (BIA) to assess changes in body composition during moderate weight loss in obese subjects. METHODS: Estimates of changes in fat mass (FM) and fat-free mass (FFM) by BIA were compared with those by dual-energy X-ray absorptiometry (DXA) as the reference method during a 10-week standardized weight-loss intervention. In obese women (age: 20-50 years, mean BMI: 33.8 kg/m(2)) participating in a European multicentre trial (nutrient-gene interactions in human obesity [NUGENOB]), body composition was assessed by BIA (Bodystat QuadScan 4000) and DXA (Lunar DPX-IQ at two centres, Hologic QDR 2000 at another centre) at baseline (n=131) and at week 10 (n=105) after a mean weight loss of -5.7 kg. RESULTS: At baseline, BIA significantly overestimated FFM and underestimated FM (by 1-3 kg on average) compared with DXA, and the limits of agreement were wide (mean ± 7-8.5 kg). For body-composition changes, although biases were generally non-significant, the limits of agreement were also wide (mean ± 3.7-4.6 kg). An FFM prediction equation for BIA data was developed in subjects scanned with Lunar instruments and cross-validated in an independent sample of 31 obese women undergoing similar weight loss. However, no major improvement in limits of agreement was found. CONCLUSION: During moderate diet-induced weight loss, the use of BIA leads to estimates of changes in body composition at the individual level that can differ substantially from those assessed by DXA, indicating that BIA and DXA cannot be used interchangeably. However, BIA in this context may be used for assessing changes in body composition at group level.

[Validation of the French version of the Body Shape Questionnaire]. / Etude de validation de la version française du Body Shape Questionnaire.

UNLABELLED: In today's societies, pressures from the idea of thinness are omnipresent and lead to a corporal dissatisfaction with an excessive preoccupation of the body's image. It seems important to have, in France, a device that can evaluate the corporal dissatisfaction degree, for the reason that the troubles of the body's image is a common diagnostical category to the anorexia and bulimia (DSM IV, 1994). Cooper et al. (1987) have developed one-dimensional questionnaire of 34 items in order to measure the worries towards the weight and the shape of the body, called the "Body Shape Questionnaire" (BSQ). Its concurrent validity has been shown with the using of the corporal dissatisfaction under-scale of the Eating Disorders Inventory (EDI; Garner et Olmsted, 1984) and the using of the diagnostical questionnaire: Eating Attitude Test (EAT; Garner et Garfinkel, 1979). The BSQ gives us a way to explore the role of extreme worries towards the body's apparence in the development, the keeping and the treatment of eating disorders. From this point the BSQ is a tool widely used on an international level in researches on the eating disorders. It has been validited in Spain and in Germany whereas it has not been yet subject to a validation in France. For this reason, we proposed to use the BSQ on the french population. METHODOLOGY: The sample is made of 242 university girl students. The average age is 20.7 years old with an standard deviation of 2.26. The size and the weight helped us to calculate the Body Mass Index (BMI) which is in fact the weight divided by the size squared. The average BMI is 21.06 kg/m2 +/- 2.87. Regarding the evaluating devices, the BSQ is presented as a scale of 34 items marked by 6 different points: 1 never, 2 barely, 3 sometimes, 4 often, 5 very often, 6 always. After getting the authorization form the authors to respect during these kinds of procedures, we have started validation. The corporal dissatisfaction under-scale of Eating Disorder Inventory (EDI, Garner et al., 1991) is made of 9 items and has a scale of 6 points going from "never" to "always". In order to evaluate the accuracy of the Body Shape Questionnaire (BSQ) in France, we made a test/retest. The concurrent validity of the BSQ has been evaluated by the EDI. The 242 subjects have been asked to fill in both questionnaires during the test and the re-test (4 weeks after the test). We have evaluated the accuracy of the BSQ with the calculation of the constancy test/retest (Pearson's r) and the measure of the internal consistency (Cronbach's alpha). Then, we tested the validity regarding an external criteria. The validation procedure is based here on an examination of the correlations between the tests results (BSQ) and another measure taken as criteria (EDI). The solutions proposed by the factorial exploratory analysis have been tested by confirmatory analysis using the 2 index of adjustment: the GFI ("Goodness of Fit Index") and the CFI (Comparative Index of Bentler) which, greater than 0.85, shows a satisfying adjustment and the RMC (redidue) which has to be less than 0.10 for a satisfying adjustment. Finally, inferential statistical analysis have studied the relations between the weight's category and the total result at the BSQ and the results of the factors sprung from factorial analysis. RESULTS: Correlations between the items of test/re-test BSQ are greater than 0.93. The alpha coefficient is high for the test (0.95) and also for the re-test (0.94). This shows a very good internal consistency between the 34 items of the BSQ. Concerning the EDI, the correlation between the test/re-test are greater than 0.98. The alpha coefficient of Cronbach is high: 0.85 for the test and 0.84 for the re-test. The Pearson's r of the BSQ/EDI test and the BSQ/EDI re-test greater than 0.7 point out the concomitant validity of the BSQ with the EDI. We made a factorial analysis of the BSQ (test) on the 242 subjects. We used the extraction of the main components method with the extraction's rule of the curve for the real values. The transformation method used here is the normalised Varimax. The factorial analysis shows four factors with their own value greater or equal to 1 (15.1; 1.77; 1.48; 1.08). This solution concerning these four factors explains 55.2% of the total variance. The oblical rotations analysis of the four factors seems to point out a high correlation between these latters (from 0.54 to 0.77), this suggests a hierarchical pattern with a single factor which is confirmed with an Cronbach's alpha of 0.95. Then, we chose to gather around each selected factors the items presenting a substantial saturation, greater than or equal to 0.5 and which are saturated by only one factor. The first factor obtained by the factorial analysis of the BSQ has been called "social avoidance and shame of the exposure of the body". The internal coherence of this factor is satisfactory (Cronbach's alpha = 0.87). The second factor obtained has been called "body dissatisfaction compared to the lower parts ot the body (Cronbach's alpha = 0.90). The third factor has been called "using laxatives and vomiting in order to reduce body dissatisfaction" The fourth factor has been called "unsuited cognitions and behaviours in order to control the weight (Cronbach's alpha = 0.76). The solution with 1 and 4 factors has been tested by a confirmatory analysis. The adjustment parameters of the unifactorial pattern were not satisfactory (GFI = 0.76, CFI = 0.83, RMC = 0.5). The 4 factors pattern adjusted better to the data (GFI = 0.86, CFI = 0.90, RMC = 0.5). In order to determinate the differences between the weight/score categories to the BSQ) score in comparison to the 4 factors (coming from the factorial analysis), several Anova have been released as well as post-hoc tests (test of Sheffé). There is a significant effect of the weight category on the corporal dissatisfaction (BSQ result), F (2.230) = 11.34; p < 0.0001. Scheffe's test placed in a prominent position the fact that the subjects having an overweight (99.85 +/- 31.34) have a corporal dissatisfaction significantly greater than the subjects having a normal weight (74.08 +/- 27.94) and presenting a thinness (63.19 +/- 23.61). We pointed out a significant effect of the weight category on factor one "social avoidance and shame of the exposure of the body" [F (2.232) = 20.18; p < 0.001], on factor 2 "body dissatisfaction compared to the lower parts of the body" [F (2.232) = 6.38; p < 0.005] and factor 4 "reduce body dissatisfaction and unsuited cognitions and behaviours in order to control the weight" [F (2.232) = 5.67; p < 0.005]. However, there is no effect in the weight category for factor 3 "using laxatives and cominting in order to reduce the corporal dissatisfaction" [F (2.232) = 5.67; p > 0.05]. Sheffe's test highlighted the fact that the subjects having overweight have a result more important than the ones having a normal weight and presenting a thinness for factor 1.2 and 4. DISCUSSION: The BSQ "French version" seems in fact to present the same metrical qualities than its original Anglo-Saxon and Spanish versions. The concluding results invite us to continue our study of the BSQ including in our patients, the bulimic subjects and the ones who are worried about corporal aspect. Its implications on the clinical field could be really interesting especially on people suffering from the eating disorders. Then, the BSQ could provide us a way to explore the role of an extreme worry of the body's appearance in the development, the maintenance and the treatment of the eating disorders.

Effect of preparation convergence on retention and seating discrepancy of complete veneer crowns.

The purpose of this study was to evaluate the retention and marginal seating discrepancy of complete veneer crown cemented with zinc phosphate cement using various preparation convergence designs. The method employed was that of cementing cast metal crowns onto 46 metal dies fabricated as complete veneer crown preparations with various convergence angles ranging from 0 degrees to 70 degrees and a shoulder finish line. The marginal discrepancy was calculated by measuring the change in crown height before and after cementation using an optical measuring microscope. The force required to remove the crowns from the dies in a vertical direction was determined using an Instron universal testing machine and recorded as retention. The increase in preparation convergence exhibited a wide variation of seating discrepancy between specimens, ranging from 4.58 +/- 1.13 to 73.13 +/- 78.32 microm. Significant tilting of crown was observed as the convergence angle of preparation increased. The retention values ranged from 4.03 +/- 0.61 to 12.12 +/- 0.33 MPa. The Pearson analysis revealed statistically significant correlations between preparation convergence and marginal discrepancy (r = +0.62), and retention (r = -0.91). Crown retention and marginal discrepancy were influenced by the preparation convergence design.

Effect of preparation convergence on retention and seating discrepancy of complete veneer crowns.

The purpose of this study was to evaluate the retention and marginal seating discrepancy of complete veneer crown cemented with zinc phosphate using various preparation convergence designs. The method employed was that of cementing cast metal crowns onto 46 metal dies fabricated as complete veneer crown preparations with various convergence angles ranging from 0 degrees to 70 degrees and a shoulder finish line. The marginal discrepancy was calculated by measuring the change in crown height before and after cementation using an optical measuring microscope. The force required to remove the crowns from the dies in a vertical direction was determined using an Instron universal testing machine and recorded as retention. The increase in preparation convergence exhibited a wide variation of seating discrepancy between specimens, ranging from 4.58 +/- 1.13 to 73.13 +/- 78.32 microm. Significant tilting of crown was observed as the convergence angle of preparation increased. The retention values ranged from 4.03 +/- 0.61 to 12.12 +/- 0.33 MPa. The Pearson analysis revealed statistically significant correlations between preparation convergence and marginal discrepancy (r = +0.62), and retention (r = -0.91). Complete veneer crown retention and marginal discrepancy were influenced by the preparation convergence design.

[How to define and to analyse troubles of eating behaviours?]. / Comment définir et analyser les troubles des conduites alimentaires?

Eating disorders are frequent in obese patients, and often underreported. However, it is mandatory to diagnose and to assess them, as therapeutic management of these eating disorders should precede weight loss attempts. We describe the main eating disorders, their diagnosis and assessment, as well as the important steps of the management strategy, in which cognitive-behavioural therapy should play a major role.

[Factorial analysis and internal consistency of the French version of the Toronto Alexithymia Scale (TAS 20), in obese women]. / Alexithymie et obésité: étude de la structure factorielle et de la consistance interne de la version française de la Toronto Alexithymia Scale (TAS 20) chez les femmes obèses.

The term alexithymia is derived from the Greek and means no words for feeling and is used to describe a personality trait characterized by the inability to experience and express emotion. Alexithymia is a relevant feature in subjects with eating disorders. The Toronto Alexithymia Scale (TAS) is the more used scale to assess alexithymia. The TAS 20 represents the latest revised and short version of the TAS, with psychometric properties clearly superior to the other alexithymia scales. The TAS 20 is a 20-items self-administered questionnaire including three subscales: ability to identify feelings, ability to describe feelings and externally oriented thinking. The TAS 20 was sparsely used in obese people and its validity was not studied at the present time in this specific population. The aim of this study was to assess the internal consistency and the factorial structure of the TAS 20 in a group of obese women. Method-The TAS 20 was administered to 192 obese women willing to loose weight, aged from 18 to 60 years. Their body mass index (BMI) was ranged from 27.5 to 55,0 kg/m2. The patients also completed a depression scale (Beck Depression Inventory 13). Cronbach's alpha coefficient was used to investigate the internal consistency of the scale. A confirmatory factorial analysis was performed to examine the validity of the initial three-factor structure in this population. The confirmatory factor analysis was conducted using STATISTICA 5.0((R)). Results-An exploratory factorial analysis using the principal components method was performed to search for a more relevant factorial structure. The global internal consistency value (a) was 0,74 for the full scale. The a coefficients were 0.78 and 0.67 respectively, for the two first subscales, (ability to identify feelings and ability to describe feelings), but was low (a=0.33) for the last subscale (externally oriented thinking). This result questionned the initial three-factor solution and conducted us to perform a exploratory factorial analysis. This analysis yielded a six factors solution, explaining 58.7% of the total variance, with the sole item 3 forming the sixth factor. The factor analysis yielding a five factors solution was retained. This solution explained 53.6% of the total variance. The first factor (22.3% of the variance) was constituted by the majority of the first subscale's items (items 1, 3, 6, 7, 9, 11, 13, 14) and corresponded to the ability to identify feelings. Four items out of five of the second dimension ability to describe feelings (items 2, 4, 12, 17) constituted the fourth factor (7.1% of the variance) of the analysis. The third subscale (externally oriented thinking) was divided in three factors explaining respectively 10.7%, 7.5% and 6.0% of the variance. The first of them included the items 5, 10 and 18, the second one included the items 15, 16 and 20, and the last one included the items 8 and 19. We called these three factors emotional avoidance , lack of interest in psychological comprehension and cognitive avoidance , respectively. The parameter estimates of the confirmatory factorial analysis for this five-factor solution were: c(2) goodness-of-fit=287.50 (df=141; p<0.001), goodness-of-fit-index=0.87, adjusted goodness-of-fit index=0.82, root-mean-square-residual=0.08. The different models were compared by testing the differences in the chi-squares. The five-factor solution was better than the other tested models. Discussion-The results of the present study indicate that the use of the TAS 20 to assess alexithymia in obese subjects willing to loose weight, requires a careful interpretation related to the features of this population. Exploratory factorial analysis suggests a five factors solution statistically and clinically more relevant than the three factors solution. The first dimension (ability to identify feelings) is retained. The second dimension (ability to describe feelings) could rather be linked to the common wishes of obese women to keep their own feelings to themselves than to a dimension of alexithymia. Our data suggest to t to divide the last initial dimension externally oriented thinking in three independant factors which we named: emotional avoidance , cognitive avoidance and lack of interest in psychological comprehension . Emotional and cognitive avoidance could be linked to the fact that our subjects wanted to loose weight and exhibited restrain eating. A positive correlation between restrain eating and alexithymia was previously reported. The last factor lack of interest in psychological comprehension would constitute an actual dimension of alexithymia: former studies found a negative correlation between alexithymia and psychologically oriented thinking.

[Effect of nutrition on adipose tissue metabolism in humans]. / Vliv výzivy na metabolismus tukové tkáne u cloveka.

Lipolysis in adipose tissue and balance between energy intake and expenditure are involved in the regulation of adipose tissue mass. Several recent findings suggest that alterations in the regulation of lipolysis and/or energy balance might contribute to the development of obesity. Hormone-sensitive lipase and uncoupling proteins play important role in regulation of lipolysis in adipose tissue as well as in the regulation of energy balance of various tissues. Mechanisms of the control of expression of genes coding synthesis of these proteins are poorly known. A brief overview of the present knowledge of the effects of nutritional intervention on the regulation of lipolysis in adipose tissue and on the expression of genes of hormone-sensitive lipase and that of uncoupling proteins is given in this article. Results of the authors' studies on the effect of calorie restriction on gene expression in adipose tissue are presented.

Triiodothyronine-mediated up-regulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes.

Triiodothyronine (T3) increases mitochondrial respiration and promotes the uncoupling between oxygen consumption and ATP synthesis. T3 effect is mediated partly through transcriptional control of genes encoding mitochondrial proteins. We determined the effect of T3 on mRNA levels of uncoupling proteins (UCP) and proteins involved in the biogenesis of the respiratory chain in human skeletal muscle and on UCP2 mRNA expression in adipose tissue. Ten young, healthy males received 75 to 100 5g of T3 per day for 14 days. The increase in plasma-free T3 levels was associated with an increase of resting metabolic rate and a decrease of respiratory quotient. In skeletal muscle, treatment with T3 induced a twofold increase of both UCP2 and UCP3 mRNA levels (p c oxidase subunits 2 and 4, nuclear respiratory factor 1, mitochondrial transcription factor A, and the co-activator PGC1 did not change during the treatment. In adipose tissue, UCP2 mRNA levels increased threefold. The direct effect of T3 on skeletal muscle an d adipose tissue UCP2 and UCP3 mRNA expression was demonstrated in vitro in human primary cultures. Our data show that T3 induces UCP2 and UCP3 mRNA expression in humans. In skeletal muscle, UCP regulation by T3 is not associated with the transcriptional regulation of respiratory chain proteins.

Recent developments on lipolysis regulation in humans and discovery of a new lipolytic pathway.

In man, the major hormones controlling the lipolytic function are insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). Catecholamines are of major importance for the regulation of lipid mobilization in human adipose tissue and for the increase of non-esterified fatty acid supply to the working muscle. In vitro studies have shown that there are differences in the catecholaminergic control of fat cells from various fat deposits and a number of physiological and pathological alterations of catecholamine-induced lipolysis have been reported. Lipolytic resistance to catecholamines has been reported in subcutaneous adipose tissue, the major fat depot in obese subjects. Multiple alterations in catecholamine signal transduction pathways have been reported. In situ microdialysis allows a physiological exploration of adipose tissue biology. Recent data obtained on the catecholaminergic regulation of lipolysis and lipid mobilization, using microdialysis in humans, will be analysed. A potent lipolytic and lipomobilizing effect of atrial natriuretic peptide has recently been discovered; the mechanisms of action and physiological relevance will also be discussed.

Glucose-induced sympathetic activity and energy expenditure during acute alpha2-adrenergic antagonism in obese subjects.

OBJECTIVE: To determine the effect of an alpha2-adrenoceptor antagonist, idazoxan, on the sympathetic nervous system and on energy expenditure responses after an oral glucose load, in obese patients. (idazoxan acts as an indirect sympathomimetic drug through blockade of presynaptic alpha2-adrenoceptors). DESIGN: Double-blind randomized placebo-controlled cross-over study. Idazoxan (40 mg) or placebo were administered orally 90 min before a 100 g oral glucose load. SUBJECTS: Twelve long-standing obese subjects (six men and six women, age range from 24 to 45 y, body mass index range from 30.2 to 41.3 kg/m2). MEASUREMENTS: Energy expenditure was derived from oxygen consumption and carbon dioxide production according to indirect calorimetry. Plasma samples were obtained for plasma adrenaline and noradrenaline, glucose, non-esterified fatty acid (NEFA), glycerol and insulin determinations. RESULTS: The plasma noradrenaline concentration response to the glucose load was significantly higher after idazoxan than after placebo administration. The time-course of glucose load-induced thermogenesis was not significantly different after administration of idazoxan nor placebo. Idazoxan administration did not modify the insulin, non-esterified fatty acids or glycerol concentration responses to the glucose load. Neither heart rate nor blood pressure values were modified by idazoxan when compared to placebo. However, idazoxan significantly improved glucose tolerance. CONCLUSION: The alpha2-adrenergic antagonist idazoxan increases glucose-induced sympathetic activity but not energy expenditure in obese subjects. These data do not argue for the development of alpha2AR antagonist compounds as anti-obesity treatment.

LPA as a paracrine mediator of adipocyte growth and function.

Adipogenesis corresponds to the recruitment of new adipocytes in adipose tissue, and results from the proliferation/differentiation of preadipocytes. Production of paracrine and autocrine factors by adipocytes plays an important role in adipogenesis. We recently demonstrated the existence of adipocyte production of lysophosphatidic acid (LPA) both in vitro and in situ. This production is modulated by catecholamines via alpha 2-adrenergic receptors. Adipocyte-LPA present in conditioned media increases the growth of a preadipose cell line in culture. This growth is associated with an activation of mitogen-activated protein kinases, and of the focal adhesion kinase. Because of the close proximity of preadipocytes and adipocytes within adipose tissue, adipocyte-LPA could play an important role in autocrine/paracrine control of adipogenesis.

Increase in epinephrine-induced responsiveness during microgravity simulated by head-down bed rest in humans.

The epinephrine (Epi)-induced effects on the sympathetic nervous system (SNS) and metabolic functions were studied in men before and during a decrease in SNS activity achieved through simulated microgravity. Epi was infused at 3 graded rates (0.01, 0.02, and 0. 03 microg. kg(-1). min(-1) for 40 min each) before and on the fifth day of head-down bed rest (HDBR). The effects of Epi on the SNS (assessed by plasma norepinephrine levels and spectral analysis of systolic blood pressure and heart rate variability), on plasma levels of glycerol, nonesterified fatty acids (NEFA), glucose and insulin, and on energy expenditure were evaluated. HDBR decreased urinary norepinephrine excretion (28.1 +/- 4.2 vs. 51.5 +/- 9.1 microg/24 h) and spectral variability of systolic blood pressure in the midfrequency range (16.3 +/- 1.9 vs. 24.5 +/- 0.9 normalized units). Epi increased norepinephrine plasma levels (P < 0.01) and spectral variability of systolic blood pressure (P < 0.009) during, but not before, HDBR. No modification of Epi-induced changes in heart rate and systolic and diastolic blood pressures were observed during HDBR. Epi increased plasma glucose, insulin, and NEFA levels before and during HDBR. During HDBR, the Epi-induced increase in plasma glycerol and lactate levels was more pronounced than before HDBR (P < 0.005 and P < 0.001, respectively). Epi-induced energy expenditure was higher during HDBR (P < 0.02). Our data suggest that the increased effects of Epi during simulated microgravity could be related to both the increased SNS response to Epi infusion and/or to the beta-adrenergic receptor sensitization of end organs, particularly in adipose tissue and skeletal muscle.

Uncoupling protein-2 (UCP2) and uncoupling protein-3 (UCP3) expression in adipose tissue and skeletal muscle in humans.

Uncoupling protein-2 (UCP2) and uncoupling protein-3 (UCP3) are mitochondrial proteins that may play a role in the control of energy expenditure by uncoupling respiration from ATP synthesis. The present review focuses on data obtained in humans. UCP2 is widely expressed in the body, whereas UCP3 expression is restricted to skeletal muscle. Positive correlations have been reported between UCP2 mRNA concentrations in adipose tissue, UCP3 mRNA concentrations in skeletal muscle, and components of the metabolic rate. Fasting induces an up-regulation of UCP2 and UCP3 mRNA expression. In vivo and in vitro studies suggest that fatty acids could modulate uncoupling protein gene expression. The putative relationship between obesity, energy expenditure and uncoupling protein expression, and the unexpected rise in UCP2 and UCP3 mRNA concentrations during short-term fasting, are discussed in view of the recent data obtained in rodents and cell lines.

Uncoupling protein-2 messenger ribonucleic acid expression during very-low-calorie diet in obese premenopausal women.

Uncoupling protein-2 (UCP2) is a mitochondrial protein expressed in a wide range of human tissues. By uncoupling respiration from ATP synthesis, UCP2 might be involved in the control of energy expenditure. We have investigated UCP2 gene expression in human adipose tissue. In eight subjects, we found a positive correlation (r = 0.91, P < 0.002) between subcutaneous and visceral fat depots UCP2 messenger RNA (mRNA) levels, suggesting that UCP2 mRNA level in subcutaneous adipose tissue is a good index of UCP2 gene expression in whole body adipose tissues. The effect of a 25-day very-low-calorie diet un UCP2 mRNA level and resting metabolic rate was investigated in eight obese premenopausal women. There was no difference in UCP2 mRNA levels before and during the diet. After 25 days of hypocaloric diet, a positive correlation was found between adipose tissue UCP2 mRNA level and resting metabolic rate adjusted for lean body mass (r = 0.82, P < 0.01). These results show that very-low-calorie diet, unlike short-term fasting, is not associated with an induction in UCP2 mRNA expression, and that adipose tissue UCP2 mRNA levels may be related to variations in resting energy expenditure in humans.

Catecholamine effects on lipolysis and blood flow in human abdominal and femoral adipose tissue.

With the use of the microdialysis method, the present study, performed on young, healthy, nonobese subjects of both genders, compares the effects of locally infused catecholamines on glycerol concentration and blood flow in abdominal (Abd) and femoral (Fem) adipose tissue. Physiological activation of the sympathetic nervous system through active tilt was also investigated. In both genders, extracellular glycerol concentration was higher in Fem than in Abd adipose tissue. Local blood flow was lower in Fem than in Abd adipose tissue. Isoproterenol perfusion increased extracellular glycerol levels, but no differences were found by gender or fat-deposit site. Isoproterenol induced a greater increase in local blood flow in Fem adipose tissue in both genders. Epinephrine and norepinephrine perfusion increased extracellular glycerol and reduced blood flow. No major differences were found according to gender and fat-deposit site. Active tilt increased plasma glycerol, free fatty acid, norepinephrine levels, and extracellular glycerol concentration to the same extent whatever the gender and fat deposit. Thus, Fem adipose tissue is characterized by a higher extracellular glycerol concentration and a lower blood flow than is Abd tissue in men and women. In these tissues, in situ lipolysis and local blood flow were similar in response to adrenergic stimulation.

Alpha2-adrenergic receptor-mediated release of lysophosphatidic acid by adipocytes. A paracrine signal for preadipocyte growth.

In the search for the existence of adrenergic regulation of the autocrine/paracrine function of the white adipose tissue, it was observed that conditioned media from isolated adipocytes or dialysates obtained by in situ microdialysis of human subcutaneous adipose tissue increased spreading and proliferation of 3T3F442A preadipocytes. These effects were amplified when an alpha2-adrenergic agonist was present during the obtention of conditioned media and microdialysates. This alpha2-adrenergic-dependent trophic activity was completely abolished by pretreatment of the conditioned media or microdialysates with the lysophospholipase, phospholipase B. Among the different lysophospholipids tested only lysophosphatidic acid (LPA) was able to induce spreading and proliferation of 3T3F442A preadipocytes. Moreover, previous chronic treatment of 3T3F442A preadipocytes with LPA which led to a specific desensitization of LPA responsiveness, abolished the alpha2-adrenergic-dependent trophic activities of the conditioned media and microdialysates. Finally, alpha2-adrenergic stimulation led to a rapid, sustained, and pertussis toxin-dependent release of [32P]LPA from [32P]-labeled adipocytes. Based upon these results it was proposed that in vitro and in situ stimulation of adipocyte alpha2-adrenergic receptors provokes the extracellular release of LPA leading, in turn, to regulation of preadipocyte growth.

Simulated microgravity increases beta-adrenergic lipolysis in human adipose tissue.

The effect of a sustained decrease in sympathetic nervous activity, achieved through 5-day head-down bed rest (HDBR), on the beta-adrenergic lipolytic activity of s.c. adipose tissue was studied in eight healthy men. The in situ beta-adrenoceptor (AR) sensitivity was studied using the microdialysis method. Local perfusion of increasing concentrations of isoprenaline showed an increased beta-AR sensitivity to lipolysis (assessed by extracellular glycerol concentration) and to vascular tone (assessed by the ethanol clearance). The adrenergic sensitivity of isolated adipocytes was studied in vitro. Basal lipolysis and the response to nonselective (isoprenaline) or selective (dobutamine, terbutaline, and CGP 12177) beta-AR agonists were increased after HDBR as was the lipolytic effect of dibutyryl cAMP. When data were expressed as a percentage of the dibutyryl cAMP effect to rule out the postreceptor events, basal and lipolytic responses to beta-AR agonists where similar before and during HDBR. The alpha 2-AR-mediated antilipolytic effects of adrenaline were not modified. Lymphocyte beta-AR number was unchanged during HDBR. Our results demonstrate that a sustained sympathoinhibition induces an increase in the lipolytic beta-adrenergic response in adipose tissue and suggest that this hypersensitization is linked to an increase in the postreceptor steps of the lipolytic cascade in the adipocyte rather than to changes in beta-adrenoceptors.