Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity.

BACKGROUND: Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. OBJECTIVES: To assess the effects of fructose (75 g day-1 ), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. METHODS: We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). RESULTS: Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased ß-hydroxybutyrate (a measure of ß-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. CONCLUSION: Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks.

Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men.

BACKGROUND AND AIMS: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. METHODS AND RESULTS: As many as 66 obese (BMI 26-40 kg/m2) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). CONCLUSION: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge.

Effect of adipose tissue volume loss on circulating 25-hydroxyvitamin D levels: results from a 1-year lifestyle intervention in viscerally obese men.

BACKGROUND/OBJECTIVES: Although weight loss has been associated with changes in circulating 25-hydroxyvitamin D (25(OH)D) levels, the quantification of the increase in 25(OH)D levels as a function of adipose tissue volume loss precisely assessed by imaging has not been reported before. The objective of this substudy was to describe the effects of a 1-year lifestyle intervention on plasma 25(OH)D levels. The relationships between changes in 25(OH)D levels and changes in adiposity volume (total and by adipose tissue compartment) were studied. SUBJECTS/METHODS: This intervention study was performed between 2004 and 2006 and participants were recruited from the general community. Sedentary, abdominally obese and dyslipidemic men (n=103) were involved in a 1-year lifestyle modification program. Subjects were individually counseled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500-kcal daily energy deficit and to increase physical activity/exercise habits. Body weight, body composition and fat distribution were assessed by dual-energy X-ray absorptiometry and computed tomography, whereas the 25(OH)D levels were measured with an automated assay. RESULTS: The 1-year intervention resulted in a 26% increase in circulating 25(OH)D (from 48±2 nmol l(-1) or 19±0.8 ng ml(-1) (±s.e.m.) to 58±2 nmol l(-1) or 23±0.8 ng ml(-1), P<0.0001) along with a 26% decrease in visceral adiposity volume (from 1947±458 to 1459±532 cm3). One-year increases in 25(OH)D levels correlated inversely with changes in all adiposity indices, especially Δvisceral (r=-0.36, P<0.0005) and Δtotal abdominal (r=-0.37, P<0.0005) adipose tissue volumes. CONCLUSIONS: These results indicate that there is a linear increase in circulating 25(OH)D levels as a function of adiposity volume loss, and therefore suggest a role of adiposity reduction in the management of obesity-associated vitamin D insufficiency.

Visceral, subcutaneous abdominal adiposity and liver fat content distribution in normal glucose tolerance, impaired fasting glucose and/or impaired glucose tolerance.

OBJECTIVES: To examine the specific distribution of liver fat content, visceral and subcutaneous adiposity in normal glucose tolerance (NGT/NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined conditions (IFG+IGT), as well as with newly diagnosed type 2 diabetes (nT2D). DESIGN: Multicenter, international observational study: cross-sectional analysis. SUBJECTS: Two thousand five hundred and fifteen patients (50.0% women, 54.5% non-Caucasian) without previously known diabetes were recruited from 29 countries. Abdominal fat distribution was measured by computed tomography (CT). Liver fat was estimated using the CT-liver mean attenuation. RESULTS: Compared with NGT/NGT patients, increased visceral adiposity was found in iIFG, iIGT, IFG+IGT and nT2D; estimated liver fat progressively increased across these conditions. A one-s.d. increase in visceral adiposity was associated with an increased risk of having iIFG (men: odds ratio (OR) 1.41 (95% confidence interval (CI) 1.15-1.74), women: OR 1.62 (1.29-2.04)), iIGT (men: OR 1.59 (1.15-2.01), women: OR 1.30 (0.96-1.76)), IFG+IGT (men: OR 1.64 (1.27-2.13), women: OR 1.83 (1.36-2.48)) and nT2D (men: OR 1.80 (1.35-2.42), women: OR 1.73 (1.25-2.41)). A one-s.d. increase in estimated liver fat was associated with iIGT (men: OR 1.46 (1.12-1.90), women: OR 1.81 (1.41-2.35)), IFG+IGT (men: OR 1.42 (1.14-1.77), women: OR 1.74 (1.35-2.26)) and nT2D (men: OR 1.77 (1.40-2.27), women: OR 2.38 (1.81-3.18)). Subcutaneous abdominal adipose tissue showed an inverse relationship with nT2D in women (OR 0.63 (0.45-0.88)). CONCLUSIONS: Liver fat was associated with iIGT but not with iIFG, whereas visceral adiposity was associated with both. Liver fat and visceral adiposity were associated with nT2D, whereas subcutaneous adiposity showed an inverse relationship with nT2D in women.

Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM trial.

AIMS: Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes. We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance. METHODS: After approximately 3.5 years of exposure to rosiglitazone 8 mg (n = 88) or placebo (n = 102), 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat content, total fat and lean mass were calculated and changes in levels of fasting adipokines, free fatty acids, glucose and post-load glucose were assessed. RESULTS: Compared with the placebo, participants on rosiglitazone had no difference in lean mass, had 4.1 kg more body fat (P < 0.0001) and 31 cm(2) more subcutaneous abdominal adipose tissue area (P = 0.007). Only after adjusting for total fat, participants on rosiglitazone had 23 cm² less visceral adipose tissue area (P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0 µg/ml with rosiglitazone and by 0.4 µg/ml with placebo (P < 0.0001). Rosiglitazone's effect on fat distribution was not independent of changes in adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2-h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids. CONCLUSIONS: In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone is associated with relatively less hepatic and visceral fat, increased subcutaneous fat and increased adiponectin levels. These effects do not appear to explain the glucose-lowering effect of rosiglitazone.

Weight loss and regain in obese individuals: a link with adipose tissue metabolism indices?

This study was performed to examine whether changes in subcutaneous adipose tissue (SCAT) metabolism indices after weight loss were related to the magnitude of weight regain. Nine men and ten premenopausal women whose body mass index ranged from 30 to 42 kg/m(2), 35-48 years old, were studied before and after a 15-week weight loss program, as well as at a 17-22-month follow-up period. Although body composition was evaluated at all study periods, abdominal and femoral SCAT-lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities, and Alpha2- and Beta-adrenoceptors (ARs) were measured before and after weight loss, exclusively. Although the SCAT-LPL activity did not change after weight loss in men, it tended to decrease in the femoral depot of women (p = 0.06). SCAT-HSL activity remained unchanged after weight reduction in men, while the post-weight loss lipase activity tended to be higher in both regions of women (p = 0.06). Although the post-weight loss number of β-ARs was higher irrespective of the fat depot (0.001 < p < 0.05), the number of Alpha2-ARs was increased in the femoral (p < 0.05), but not in the abdominal SCAT (p = 0.08) after weight reduction, in men. Neither the Alpha2- nor the Beta-AR density changed after weight reduction, in women. Abdominal SCAT-LPL activity after weight reduction was negatively related to weight regain indices, in women (-0.65 < Rhô < -0.75; 0.01 < p < 0.05). Both the post-weight loss abdominal SCAT Alpha 2-AR density and the Alpha 2-/Beta-AR balance were positively associated with weight regain indices, in men (0.69 < Rhô < 0.88; 0.01 < p < 0.05). These results suggest that selected SCAT metabolism indices could predict failure to weight loss maintenance, in both genders

Weight loss and regain in obese individuals: a link with adipose tissue metabolism indices?

This study was performed to examine whether changes in subcutaneous adipose tissue (SCAT) metabolism indices after weight loss were related to the magnitude of weight regain. Nine men and ten premenopausal women whose body mass index ranged from 30 to 42 kg/m(2), 35-48 years old, were studied before and after a 15-week weight loss program, as well as at a 17-22-month follow-up period. Although body composition was evaluated at all study periods, abdominal and femoral SCAT-lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities, and α2- and ß-adrenoceptors (ARs) were measured before and after weight loss, exclusively. Although the SCAT-LPL activity did not change after weight loss in men, it tended to decrease in the femoral depot of women (p = 0.06). SCAT-HSL activity remained unchanged after weight reduction in men, while the post-weight loss lipase activity tended to be higher in both regions of women (p = 0.06). Although the post-weight loss number of ß-ARs was higher irrespective of the fat depot (0.001 < p < 0.05), the number of α2-ARs was increased in the femoral (p < 0.05), but not in the abdominal SCAT (p = 0.08) after weight reduction, in men. Neither the α2- nor the ß-AR density changed after weight reduction, in women. Abdominal SCAT-LPL activity after weight reduction was negatively related to weight regain indices, in women (-0.65 < Rhô < -0.75; 0.01 < p < 0.05). Both the post-weight loss abdominal SCAT α2-AR density and the α2-/ß-AR balance were positively associated with weight regain indices, in men (0.69 < Rhô < 0.88; 0.01 < p < 0.05). These results suggest that selected SCAT metabolism indices could predict failure to weight loss maintenance, in both genders.

Assessment of cardiometabolic risk and prevalence of meeting treatment guidelines among patients with type 2 diabetes stratified according to their use of insulin and/or other diabetic medications: results from INSPIRE ME IAA.

AIM: Visceral adipose tissue (VAT) and liver fat (LF) are strongly associated with type 2 diabetes. It is not known, however, how diabetes treatment and/or risk factor management modulates the association between VAT, LF and diabetes. The aim was to determine the level of VAT and LF in patients with type 2 diabetes according to their treatment status and achievement of the American Diabetes Association's (ADA) diabetes management goals. METHODS: We performed a cross-sectional analysis of the baseline data of the International Study of the Prediction of Intra-Abdominal Adiposity and its Relationship with Cardiometabolic risk/Intra-Abdominal Adiposity (INSPIRE ME IAA), a 3-year prospective cardiometabolic imaging study conducted in 29 countries. Patients (n = 3991) were divided into four groups: (i) those without type 2 diabetes (noT2D n = 1003 men, n = 1027 women); (ii) those with type 2 diabetes but not treated with diabetes medications (T2Dnomeds n = 248 men, n = 198 women); (iii) those with type 2 diabetes and treated with diabetes medications but not yet using insulin (T2Dmeds-ins n = 591 men, n = 484 women) and (iv) those with type 2 diabetes and treated with insulin (T2Dmeds+ins n = 233 men, n = 207 women). Abdominal and liver adiposity were measured by computed tomography. RESULTS: Fewer patients with high VAT or LF achieved the ADA's goals for high-density lipoprotein cholesterol (HDL-C) or triglycerides compared to patients with low VAT or LF. Visceral adiposity (p = 0.02 men, p = 0.003 women) and LF (p = 0.0002 men, p = 0.0004 women) increased among patients who met fewer of the ADA treatment criteria, regardless of type 2 diabetes treatment. CONCLUSION: Residual cardiometabolic risk exists among patients with type 2 diabetes characterized by elevated VAT and LF.

Maternal fitness at the onset of the second trimester of pregnancy: correlates and relationship with infant birth weight.

UNLABELLED: What is already known about this subject A healthy life begins in utero and a healthy pregnancy requires a fit and healthy mother. Physical activity during pregnancy provides a stimulation that is essential for promoting optimal body oxygenation and composition as well as metabolic fitness during pregnancy. Although a higher maternal fitness is expected to provide a beneficial fetal environment, it is still unclear whether physical fitness during pregnancy contributes to perinatal health. What this study adds Participation in sports and exercise previously and at the beginning of pregnancy can benefit maternal health by improving cardiorespiratory fitness during pregnancy, irrespective of maternal body mass index. Maternal strength, an indicator of muscular fitness, is an independent determinant of infant fetal growth and can positively influence birth weight. BACKGROUND: It is still unclear whether maternal physical activity and fitness during pregnancy contributes to perinatal health. OBJECTIVES: The aims of this study were to characterize maternal physical fitness at 16 weeks of pregnancy and to examine its effects on infant birth weight. METHODS: Maternal anthropometry (body mass index [BMI] and skin-folds), physical activity, cardiorespiratory fitness (VO2 peak) and muscular fitness (handgrip strength) were assessed at 16 weeks of gestation in 65 healthy pregnant women. Offspring birth weight was collected from maternal charts after delivery. RESULTS: A higher VO2 peak was associated with physical activity spent at sports and exercise before and in early pregnancy (P = 0.0005). Maternal BMI was negatively associated with cardiorespiratory fitness (P < 0.0001) but positively related to muscular strength (P = 0.0001). Unlike maternal cardiorespiratory fitness, handgrip strength was positively associated with infant birth weight (r = 0.34, P = 0.0068) even after adjustment for confounders (adjusted r = 0.27, P = 0.0480). CONCLUSION: A positive relationship between maternal muscular fitness and infant birth weight highlighted maternal strength in pregnancy as a new determinant of infant birth weight.

Changes in plasma endocannabinoid levels in viscerally obese men following a 1 year lifestyle modification programme and waist circumference reduction: associations with changes in metabolic risk factors.

AIMS/HYPOTHESIS: We previously reported that the plasma levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), in a cohort of viscerally obese men are directly correlated with visceral adipose tissue (VAT) accumulation and metabolic risk factors including low HDL-cholesterol and high triacylglycerol. It is not known, however, if such correlations persist after vigorous lifestyle interventions that reduce metabolic risk factors. We analysed the changes in endocannabinoid levels in a subsample from the same cohort following a 1 year lifestyle modification programme, and correlated them with changes in VAT and metabolic risk factors. METHODS: Forty-nine viscerally obese men (average age 49 years, BMI 30.9 kg/m(2), waist 107.3 cm) underwent a 1 year lifestyle modification programme including healthy eating and physical activity. Plasma levels of 2-AG and the other most studied endocannabinoid, anandamide, were measured by liquid chromatography-mass spectrometry. Anthropometric and metabolic risk factors, including VAT, insulin resistance and glucose intolerance, HDL-cholesterol and triacylglycerol, were measured. RESULTS: Most risk factors were improved by the intervention, which led to a significant decrease in body weight (-6.4 kg, p < 0.0001), waist circumference (-8.0 cm, p < 0.0001) and VAT (-30%, p < 0.0001), and in plasma 2-AG (-62.3%, p < 0.0001) and anandamide (-7.1%, p = 0.005) levels. The decrease in levels of 2-AG but not those of anandamide correlated with decreases in VAT and triacylglycerol levels, and with the increase in HDL(3)-cholesterol levels. Multivariate analyses suggested that decreases in 2-AG and VAT were both independently associated with decreases in triacylglycerol. CONCLUSIONS/INTERPRETATION: This study shows that a strong correlation exists between 2-AG levels and high plasma triacylglycerol and low HDL(3)-cholesterol in viscerally obese men.

Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men.

OBJECTIVE: The link between excess intra-abdominal adiposity (IAA) and metabolic complications leading to type 2 diabetes and cardiovascular disease is well recognized. Blockade of endocannabinoid action at cannabinoid CB(1) receptors was shown to reduce these complications. Here, we investigated the relationship between IAA, circulating endocannabinoid levels and markers of cardiometabolic risk in male obese subjects. DESIGN, SUBJECTS AND MEASUREMENTS: Fasting plasma levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were measured by liquid chromatography-mass spectrometry in a study sample of 62 untreated asymptomatic men with body mass index (BMI) from 18.7 to 35.2 kg/m(2). RESULTS: Plasma 2-AG, but not AEA, levels correlated positively with BMI, waist girth, IAA measured by computed tomography, and fasting plasma triglyceride and insulin levels, and negatively with high-density lipoprotein cholesterol and adiponectin levels. Obese men with similar BMI values (> or =30 kg/m(2)) but who markedly differed in their amount of IAA (< vs > or = 130 cm(2), n=17) exhibited higher 2-AG levels in the presence of high IAA. No difference in 2-AG concentrations was observed between obese men with low levels of IAA vs nonobese controls. CONCLUSIONS: These results provide evidence for a relationship in men between a key endocannabinoid, 2-AG, and cardiometabolic risk factors, including IAA.

Contribution of CB1 blockade to the management of high-risk abdominal obesity.

The worldwide increase in the prevalence of type 2 diabetes represents a tremendous challenge for our healthcare system, especially if we consider that this phenomenon is largely explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting that abdominal adipose tissue is the fat depot that conveys the greatest risk of metabolic complications. This cluster of metabolic abnormalities has been referred to as the metabolic syndrome and this condition is largely the consequence of abdominal obesity, especially when accompanied by a high accumulation of visceral adipose tissue. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of coronary heart disease beyond the presence of traditional risk factors. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of coronary heart disease and of type 2 diabetes. The recent discovery of the endocannabinoid-CB1 receptor system and of its impact on the regulation of energy metabolism represents a significant advance, which will help physicians target abdominal obesity and its related metabolic complications. In this regard, studies have shown that rimonabant therapy (the first developed CB1 blocker) could be useful for the management of clustering cardiovascular disease risk factors in high-risk abdominally obese patients through its effects not only on energy balance but also on adipose tissue metabolism. For instance, the presence of CB1 receptors in adipose tissue and the recently reported effect of rimonabant on adiponectin production by adipose cells may represent a key factor responsible for the weight loss-independent effect of this CB1 blocker on cardiometabolic risk variables.

Relationship between severity of nocturnal desaturation and adaptive thermogenesis: preliminary data of apneic patients tested in a whole-body indirect calorimetry chamber.

The purpose of this study was to investigate the possibility of a relationship between the severity of obstructive sleep apnea syndrome (OSAS) and adaptive thermogenesis. Daily energy expenditure (DEE) and sleeping metabolic rate (SMR) were measured in apneic and a priori nonapneic subjects who were tested in a whole-body indirect calorimetry chamber for 24 h. The apneic patients were diagnosed by nocturnal home oximetry to determine the percentage of total recording time spent below 90% arterial oxygen saturation (% TRT <90% SaO(2)). Reference equations established from body weight and age in nonapneic subjects were used to predict DEE and SMR in apneic patients. The predicted values of the apneic patients were then compared to their measured values. No significant difference was found between predicted and measured values in SMR nor in DEE. We observed a significant relationship between the severity of nocturnal desaturation and the difference between predicted and measured DEE in apneic patients (r = -0.74, P < 0.05) and a similar negative trend with SMR (r = -0.65, P = 0.08). These preliminary data suggest that a nocturnal hypoxia may influence adaptive thermogenesis in apneic patients and complicate their body weight regulation.

Estimation of daily energy needs with the FAO/WHO/UNU 1985 procedures in adults: comparison to whole-body indirect calorimetry measurements.

OBJECTIVES: To measure daily energy expenditure (DEE) with indirect calorimetric facilities in sedentary and active subjects. To estimate daily energy needs with the FAO/WHO/UNU (1985) procedures (EDEE) and estimated energy requirement (EER) with the dietary reference intakes 2002 (DRI) in healthy adults with sedentary or high-activity conditions. To compare estimated daily energy needs with their measured values. DESIGN: Two groups of healthy subjects were tested under sedentary or high-activity conditions. In both groups, resting energy expenditure was measured after a 12-h overnight fast. DEE and basal metabolic rate (BMR) values were also measured with indirect calorimetry and compared to the relevant predicted values. Physical activity level and BMR were also estimated. SUBJECTS: A total of 45 sedentary (26 men and 19 women) and 69 active subjects (43 men and 26 women) aged 18-30 and 30-60 y. RESULTS: Measured daily energy expenditure (MDEE) was significantly lower than EDEE in sedentary men and women and in active men for the two age groups considered (P<0.05). EER was significantly lower than EDEE in both sedentary and active subjects of each subgroup (P<0.05). CONCLUSIONS: The FAO/WHO/UNU (1985) procedures may overestimate daily energy needs, particularly in sedentary individuals. However, DRI (2002) are probably more adapted to estimate real daily energy needs in sedentary and active subjects in comparison to the FAO/WHO/UNU (1985) procedures.

Reduction of visceral adipose tissue during weight loss.

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

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

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

Is the relationship between adipose tissue and waist girth altered by weight loss in obese men?

OBJECTIVE: The aim of the present study was to examine whether the association of waist girth to visceral adipose tissue (AT) accumulation was altered by weight loss in abdominally obese men. RESEARCH METHODS AND PROCEDURES: We studied 45 dyslipidemic abdominally obese men (45.4 +/- 6.2 years of age; body mass index [BMI], 31.3 +/- 3.0 kg/m(2); waist circumference, 103.4 +/- 7.6 cm; total cholesterol, <6.72 mM; triglycerides, > or =1.7 mM but < or =5.65 mM; high density lipoprotein cholesterol, < or =1.2 mM). Each of them followed nutritional recommendations combined with a prescription of gemfibrozil (1200 mg/d) or a placebo for 1 year. After 6 months, a training exercise program was added at a frequency of four sessions of 60 minutes per week at 50% of maximal oxygen uptake. RESULTS: In response to the 1-year intervention program, men showed significant reductions in body weight, BMI, waist circumference, and in the partial volume of visceral and abdominal subcutaneous AT measured from two abdominal computed tomography scans performed at lumbar vertebra (L)2 to L3 and L4 to L5 levels. No change in waist-to-hip ratio was observed. Changes in visceral AT were strongly correlated with changes in body weight, BMI, and waist circumference (0.83 < r < 0.85; p < 0.001). However, a weak association was noted between waist-to-hip ratio and changes in visceral AT (r = 0.40; p < 0.05). There was no change in slopes or in intercepts before and after treatment in the relationships between volume or area of abdominal AT and anthropometric markers. DISCUSSION: Despite a greater level of the partial volume of subcutaneous AT than of the partial volume of visceral AT at baseline (p < 0.001), the greater relative reduction in the visceral AT volume in comparison with the subcutaneous AT volume suggested a preferential mobilization of visceral AT with weight loss in these abdominally obese men. The close relationship between changes in the partial volume of visceral AT and changes in cross-sectional areas of visceral AT measured at L2 to L3 (r = 0.94; p < 0.001) or L4 to L5 (r = 0.88; p < 0.001) suggests that a single computed tomography scan performed at L2 to L3 or L4 to L5 could predict changes in the partial volume of visceral AT secondary to weight loss.

Evidence for the existence of adaptive thermogenesis during weight loss.

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

Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity.

Recent studies have suggested that elevated plasma C-reactive protein (CRP) levels are associated with the features of insulin resistance syndrome. In the present study, we have examined the contribution of body composition measured by hydrostatic weighing and of abdominal adipose tissue (AT) accumulation assessed by computed tomography to the variation in plasma CRP levels associated with atherogenic dyslipidemia of the insulin resistance syndrome in a sample of 159 men, aged 22 to 63 years, covering a wide range of adiposity (body mass index values from 21 to 41 kg/m(2)). Plasma CRP levels showed positive and significant correlations with body fat mass (r=0.41, P<0.0001), waist girth (r=0.37, P<0.0001), and visceral AT accumulation measured by computed tomography at L4 to L5 (r=0.28, P<0.0003). Although CRP levels were associated with plasma insulin levels measured in the fasting state and after a 75-g oral glucose load, no significant correlations were found with plasma lipoprotein levels. Finally, comparison of body fatness, of abdominal fat accumulation, and of the features of the insulin resistance syndrome across quintiles of CRP revealed major differences in body fatness and in indices of abdominal AT accumulation between the lowest and the highest CRP quintiles, whereas no significant differences were found for variables of the plasma lipoprotein-lipid profile. These results suggest that obesity and abdominal AT accumulation are the critical correlates of elevated plasma CRP levels found in men with atherogenic dyslipidemia of the insulin resistance syndrome.

Deterioration of the metabolic risk profile in women. Respective contributions of impaired glucose tolerance and visceral fat accumulation.

OBJECTIVE: To determine whether the impaired glucose tolerance (IGT) state contributes to the deterioration of the metabolic profile in women after taking into account the contribution of visceral adipose tissue (AT) accumulation, as measured by computed tomography. RESEARCH DESIGN AND METHODS: We studied 203 women with normal glucose tolerance (NGT) and 46 women with IGT, defined as a glycemia between 7.8 and 11.1 mmol/l measured 2 h after a 75-g oral glucose load. RESULTS: Women with IGT were characterized by a higher visceral AT accumulation and by higher concentrations of fasting plasma glucose, insulin, and C-peptide as well as by higher plasma concentrations of cholesterol, triglycerides, and apolipoprotein B (apoB) and by greater cholesterol-to-HDL-cholesterol ratio, reduced LDL peak particle size, lower HDL-cholesterol and HDL2-cholesterol concentrations, and higher blood pressure (P < 0.01) than women with NGT. When we matched 27 pairs of women for visceral AT and fat mass as well as for menopausal status, differences previously found in LDL-cholesterol, LDL peak particle size, HDL-cholesterol, and HDL2-cholesterol concentrations as well as in the cholesterol-to-HDL-cholesterol ratio and blood pressure were eliminated, whereas triglyceride concentrations remained significantly higher in women with IGT. CONCLUSIONS: A high visceral AT accumulation is a major factor involved in the deterioration of many metabolic variables in women with IGT, with the notable exception of triglyceride concentrations, which remained significantly different between women with NGT and women with IGT after adjustment for visceral fat.