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.

Parental eating behavior traits are related to offspring BMI in the Québec Family Study.

OBJECTIVE: Parental eating behavior traits have been shown to be related to the adiposity of their young children. It is unknown whether this relationship persists in older offspring or whether rigid or flexible control are involved. The objective of this study was to test the hypothesis that parental eating behavior traits, as measured by the Three-Factor Eating Questionnaire (TFEQ), are related to offspring body weight. METHODS: Cross-sectional anthropometric and TFEQ data from phase 2 and 3 of the Québec Family Study generated 192 parent-offspring dyads (offspring age range: 10-37 years). Relationships were adjusted for offspring age, sex and reported physical activity, number of offspring per family and parent body mass index (BMI). RESULTS: In all parent-offspring dyads, parental rigid control and disinhibition scores were positively related to offspring BMI (r=0.17, P=0.02; r=0.18, P<0.01, respectively). There were no significant relationships between cognitive restraint (P=0.75) or flexible control (P=0.06) with offspring BMI. Regression models revealed that parent disinhibition mediated the relationship between parent and offspring BMI, whereas rigid control of the parent moderated this relationship. The interaction effect between parental rigid control and disinhibition was a significant predictor of offspring BMI (ß=0.13, P=0.05). CONCLUSION: Family environmental factors, such as parental eating behavior traits, are related to BMI of older offspring, and should be a focus in the prevention of obesity transmission within families.

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.

Hypoadiponectinemia is associated with valvular inflammation and faster disease progression in patients with aortic stenosis.

OBJECTIVES: Adiponectin is a protein secreted by adipocytes which has anti-inflammatory properties. The objective of this study was to examine the relationship between adiponectinemia and the hemodynamic progression of aortic stenosis (AS) as well as the degree of inflammation in the valve explanted at the time of aortic valve replacement (AVR). METHODS: The plasma level of adiponectin was measured in 122 patients undergoing AVR. The explanted aortic valves were analyzed and the density of leukocytes (CD45+), T cells (CD3+) and blood vessels (von Willebrand factor positive; vWF+) was documented. Also, a subset of patients (n = 67) had ≥2 echocardiographic studies separated by at least 6 months, thereby allowing assessment of the rate of progression of stenosis during the preoperative period. RESULTS: Patients with lower plasma levels of adiponectin (<5.4 µg/ml) had a faster progression rate of the mean transvalvular gradient before surgery than those with higher levels (9 ± 1 vs. 4 ± 1 mm Hg/year; p = 0.008). Moreover, these patients with hypoadiponectinemia had significantly more leukocytes (CD45+), T cells and blood vessels (vWF+) in their explanted valves compared to those with higher adiponectin levels. CONCLUSION: These findings support the concept that adiponectin may play a protective role against the inflammatory process and progression of calcific AS.

The Three-Factor Eating Questionnaire and BMI in adolescents: results from the Québec family study.

Eating behaviour traits are associated with body weight variations in adults. The Three-Factor Eating Questionnaire (TFEQ) measures cognitive restraint, disinhibition and hunger, as well as their corresponding subscales, e.g. rigid and flexible control. The TFEQ has not been widely used in adolescents to investigate eating behaviour traits associated with body weight. The aim of the present study was to assess whether eating behaviour traits were associated with BMI in male and female adolescents. Sixty adolescents (thirty females and thirty males; mean age 15.0 (sd 2.4) years) from the Québec Family Study completed the TFEQ and 3 d dietary records. There were no sex differences in the TFEQ scores. Rigid control, disinhibition and emotional susceptibility (to overeat) were positively related to BMI z-scores for the entire sample (r 0.3, P < 0.05). There was a positive relationship between BMI z-scores and rigid control (r 0.39, P < 0.05) in females, while BMI z-scores were positively related to emotional susceptibility (r 0.42, P < 0.02) and disinhibition (r 0.41, P < 0.03) in males. Adolescents characterised by both high disinhibition and high rigid control had significantly higher BMI z-scores than those by both low disinhibition and low rigid control. There were no significant differences in BMI z-scores between the flexible control categories. Dietary macronutrient content was not consistently related to eating behaviour traits. These results show that the eating behaviour traits of disinhibition and rigid control are independently related to BMI z-scores in this group of adolescents.

Obesity, inflammation, and cardiovascular risk.

Obesity, a highly prevalent condition, is heterogeneous with regard to its impact on cardiovascular disease (CVD) risk. Epidemiological observations and metabolic investigations have consistently demonstrated that the accumulation of excess visceral fat is related to an increased risk of CVD as well as several metabolic and inflammatory perturbations. In the past decade, data from several studies have served to emphasize that atherosclerosis has an inflammatory component that may contribute to several key pathophysiological processes. Study data have also highlighted the finding that the expanded visceral fat is infiltrated by macrophages that conduct "cross-talk" with adipose tissue through several significant mechanisms. In this review, we provide, in the context of CVD risk, an up-to-date account of the complex interactions that occur between a dysfunctional adipose tissue phenotype and inflammation.

Physical inactivity, abdominal obesity and risk of coronary heart disease in apparently healthy men and women.

OBJECTIVE: To test the hypothesis that for any given body mass index (BMI) category, active individuals would have a smaller waist circumference than inactive individuals. Our second objective was to examine the respective contribution of waist circumference and physical inactivity on coronary heart disease (CHD) risk. DESIGN: Prospective, population-based study with an 11.4-year follow-up. SUBJECTS: A total of 21 729 men and women aged 45-79 years, residing in Norfolk, UK. METHODS: During follow-up, 2191 CHD events were recorded. Physical activity was evaluated using a validated lifestyle questionnaire that takes into account both leisure-time and work-related physical activity. Waist circumference was measured and BMI was calculated for each participant. RESULTS: For both men and women, we observed that within each BMI category (<25.0, 25-30 and >or=30.0 kg m(-2)), active participants had a lower waist circumference than inactive participants (P<0.001). In contrast, within each waist circumference tertile, BMI did not change across physical activity categories (except for women with an elevated waist circumference). Compared with active men with a low waist circumference, inactive men with an elevated waist circumference had a hazard ratio (HR) for future CHD of 1.74 (95% confidence interval (CI), 1.34-2.27) after adjusting for age, smoking, alcohol intake and parental history of CHD. In the same model and after further adjusting for hormone replacement therapy use, compared with active women with a low waist circumference, inactive women with an elevated waist circumference had an HR for future CHD of 4.00 (95% CI, 2.04-7.86). CONCLUSION: In any BMI category, inactive participants were characterized by an increased waist circumference, a marker of abdominal adiposity, compared with active individuals. Physical inactivity and abdominal obesity were both independently associated with an increased risk of future CHD.

Lipid-mediated inflammation and degeneration of bioprosthetic heart valves.

BACKGROUND: The durability of bioprosthetic valves is limited by structural valve degeneration (SVD) leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that a lipid-mediated inflammatory mechanism is involved in the SVD of BPs. MATERIAL AND METHODS: Eighteen Freestyle stentless BP valves were explanted for SVD at a mean time of 5.9 +/- 3 years after implantation and were analysed by immunohistochemistry and transmission electron microscopy (TEM). RESULTS: The mean age of the patients was 65 +/- 8 years and there were 11 male and seven female patients. Two of the 18 BPs had macroscopic calcification, whereas the other valves had minimal or no macroscopic calcification. Tears at the commissures leading to regurgitation was present in 16 BPs. Immunohistochemistry showed the presence of oxidized low-density lipoprotein (ox-LDL) and glycosaminoglycans in the fibrosa layer of 13 BPs. Areas with ox-LDL were infiltrated by macrophages (CD68(+)) co-expressing the scavenger receptor CD36 and metalloproteinase-9 (MMP-9). Zymogram showed the active form of MMP-9 within explanted BPs. EM studies revealed the presence of lipid-laden cells featuring foam cells and fragmented collagen. Nonimplanted control BPs obtained from the manufacturer (n = 4) had no evidence of lipid accumulation, inflammatory cell infiltration or expression of MMP9 within the leaflets. CONCLUSIONS: These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.

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.

Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis.

INTRODUCTION: Aortic stenosis (AS) is the most common valvular heart disease in westernized societies. AS is a disease process akin to atherosclerosis in which calcification and tissue remodelling play a crucial role. In patients with moderate/severe AS, we sought to determine whether the remodelling process would be in relationship with transvalvular gradients and circulating oxidised low-density lipoprotein (ox-LDL) levels. METHODS: In 105 patients with AS, the aortic valve and blood plasma were collected at the time of valve replacement surgery. The degree of valve tissue remodelling was assessed using a scoring system (Score: 1-4) and the amount of calcium within the valve cusps was determined. The standard plasma lipid profile, the size of LDL particles and the plasma level of circulating ox-LDL (4E6 antibody) were determined. RESULTS: After adjustment for covariables, aortic remodelling score was significantly related to transvalvular gradients measured by Doppler echocardiography before surgery. Patients with higher valve remodelling score had higher circulating ox-LDL levels (score 2: 27.3 (SEM 2.6) U/l; score 3: 32.2 (SEM 2.3) U/l; score 4: 38.3 (SEM 2.3) U/l; p = 0.02). After correction for age, gender, hypertension and HDL-C, the plasma level of ox-LDL remained significantly associated with the aortic valve remodelling score (p<0.001). The plasma level of ox-LDL was significantly associated with LDL-C (r = 0.41; p<0.001), apoB (r = 0.59; p<0.001), triglyceride (r = 0.39; p<0.001), Apo A-I (r = 0.23; p = 0.01) and cholesterol in small (<255 A) LDL particles (r = 0.22; p = 0.02). After correction for covariables, circulating ox-LDL levels remained significantly associated with apoB (p<0.001) and triglyceride (p = 0.01) levels. CONCLUSION: Increased level of circulating ox-LDL is associated with worse fibrocalcific remodelling of valvular tissue in AS. It remains to be determined whether circulating ox-LDL is a risk marker for a highly atherogenic profile and/or a circulating molecule which is actively involved in the pathogenesis of calcific aortic valve disease.

The 'valvulo-metabolic' risk in calcific aortic valve disease.

Calcific aortic stenosis (AS) has been considered a degenerative and unmodifiable process resulting from aging and 'wear and tear' of the aortic valve. Over the past decade, studies in the field of epidemiology, molecular biology and lipid metabolism have highlighted similarities between vascular atherosclerosis and calcific AS. In particular, work from the Quebec Heart Institute and from that of others has documented evidence of valvular infiltration by oxidized low-density lipoproteins and the presence of inflammatory cells, along with important tissue remodelling in valves explanted from patients with AS. Recent studies have also emphasized the role of visceral obesity in the development and progression of AS. In addition, visceral obesity, with its attendant metabolic complications, commonly referred to as the metabolic syndrome, has been associated with degenerative changes in bioprosthetic heart valves. The purpose of the present review is to introduce the concept of 'valvulo-metabolic risk' and to provide an update on the recent and important discoveries regarding the pathogenesis of heart valve diseases in relation to obesity, and to discuss how these novel mechanisms might translate into clinical practice.

Apolipoprotein E and lipoprotein lipase gene polymorphisms interaction on the atherogenic combined expression of hypertriglyceridemia and hyperapobetalipoproteinemia phenotypes.

The combination of hypertriglyceridemia (hyperTG) and hyperapobetalipoproteinemia (hyperapoB) is associated with an increased coronary artery disease (CAD) risk. Apolipoprotein (apo) E and lipoprotein lipase (LPL) genes are involved in the catabolism of triglycerides (TG)-rich apoB-containing lipoproteins (VLDL). Several apoE and LPL gene variants affecting CAD risk, plasma TG or apoB concentrations have an allelic frequency of >5% in the general population. This study examined the combined effect of frequent apoE and LPL gene polymorphisms on the expression of hyperTG and hyperapoB. ApoE (E2, E3, and E4) and LPL (D9N, N291S, G188E, and P207L) were genotyped and fasting lipid profiles were assessed among 1,441 French-Canadian subjects. Multivariate analyses were performed to estimate the relationship between apoE and LPL gene variants and the risk of hyperTG (TG>1.7 mmol/l) and hyperapoB (apoB>0.9 g/l). Compared to apoE3 carriers, the apoE4 allele significantly increased the risk of expressing the "hyperTG/hyperapoB" phenotype [odds ratio (OR)=1.95; p=0.014]. This risk was significantly exacerbated (OR=4.69; p=0.017) by the presence of frequent deleterious LPL gene variants in this population. The apoE2 allele was negatively associated with hyperTG/hyperapoB (OR=0.49; p=0.002) in the absence of a deleterious LPL gene variant. These results suggest that epistasis is a phenomenon to consider while assessing the CAD risk associated with gene variants or the effect of frequent alleles on high-risk lipid profiles.

Chronic effects of dehydroepiandrosterone on rat adipose tissue metabolism.

The goal of the present study was to examine cellular mechanisms that regulate adipose cell metabolism in ovariectomized (OVX) and intact rats that were subjected to long-term (27 weeks) treatment with dehydroepiandrosterone (DHEA). Forty-eight 16-month-old female rats were divided into 4 groups of 9 to 11 animals (intact, intact-DHEA, OVX, OVX-DHEA). Adipose tissue lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), and cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE) activities were determined, and alpha2-, beta1/beta2-, and beta3-adrenoceptors (ARs) were quantified. DHEA did not affect body weight, fat, or muscle mass in intact rats. The similar retroperitoneal fat pad weight of intact-DHEA rats compared to intact animals was in agreement with the lack of difference in the enzyme activities and AR densities. The increased body weight of OVX rat was paralleled by a greater retroperitoneal adipose tissue mass (P <.01), which was in turn associated with a marked rise in LPL activity (P <.005) and a slight decrease in HSL activity (P <.05) compared to intact animals. OVX-DHEA rats, compared to untreated OVX animals, had a smaller retroperitoneal fat depot, which correlated with a decrease in LPL activity (P <.005) and moderate increase in both HSL activity and beta3-AR density (P <.05). DHEA-treatment lowered fasting insulin and triglyceride levels in both intact and OVX rats (P <.05). Plasma testosterone, androsterone, androstenedione, and androstenediol levels were also significantly increased in both intact-DHEA and OVX-DHEA rats compared to untreated animals (P <.0001). These findings suggest that the antiobesity action of DHEA may be related in part to changes in lipase activities and in beta3-AR density, and that it is dependent on the ovarian status of the animal.

Effects of the FABP2 A54T mutation on triglyceride metabolism of viscerally obese men.

OBJECTIVE: Viscerally obese individuals are frequently characterized by a proatherogenic condition. A missense mutation (A54T) in the fatty acid binding protein type 2 (FABP2) gene has been associated with insulin resistance and obesity. This study examined the effect of this mutation on lipoprotein levels in viscerally obese hyperinsulinemic condition. RESEARCH METHODS AND PROCEDURES: A total of 217 men were assigned to one of two groups based on their FABP2 A54T polymorphism. RESULTS: The two genotypic groups showed no difference in either physiological characteristics or lipoprotein/lipid profile, before or after statistical adjustment for age. From this initial sample, 50 men accepted to have their postprandial lipid response assessed and 10 T54/A54 heterozygotes were then individually matched for visceral adipose tissue accumulation and fasting plasma triglyceride (TG) levels with 10 A54/A54 homozygotes. High-density lipoprotein (HDL)-TG levels were significantly increased in the fasting state as well as 4 hours after the test meal (p = 0.04 and p = 0.0008, respectively) in men bearing the A54T mutation. In addition, the area under the curve of postprandial HDL-TG levels was also significantly higher among T54/A54 heterozygotes than among A54/A54 homozygotes (p = 0.04). Interestingly, fasting TG concentrations in large TG-rich lipoproteins (large-TRL; S(f) > 400) were correlated with HDL-TG levels at 4 (r = 0.74, p = 0.01) and 8 hours (r = 0.73, p = 0.01) after the test meal in T54/A54 heterozygotes only. DISCUSSION: The FABP2 A54T missense mutation may contribute to the TG enrichment of HDL in the postprandial state that, in turn, may alter the risk of atherosclerotic vascular disease.

Age-related differences in messenger ribonucleic acid expression of key proteins involved in adipose cell differentiation and metabolism.

This study was performed to compare the expression of key proteins [lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), complement 3 (C3), and peroxisome proliferator-stimulated receptor-gamma (PPAR gamma)] involved in sc abdominal adipose tissue (AT) metabolism of young (n = 13) vs. middle-aged (n = 16) men. The sc abdominal AT-LPL activity as well as fat cell lipolysis were also measured in both groups of men. Young and middle-aged men displayed similar body weight and sc abdominal fat accumulation, measured by computed tomography. However, middle-aged men were characterized by a higher percent body fat (28 +/- 5% vs. 22 +/- 7%; P < 0.05) than young subjects. No difference between groups was observed in sc abdominal adipose tissue LPL activity. On the other hand, maximal lipolytic responses of sc abdominal adipocytes to isoproterenol (beta-adrenergic agonist) or to postadrenoceptor agents such as dibutyryl cAMP, forskolin, and theophylline were lower in middle-aged than in young men (P < 0.05). AT-LPL messenger ribonucleic acid (mRNA) levels were similar regardless of the subject's age. However, HSL, C3, and PPAR gamma mRNA levels were higher in middle-aged than in young individuals (P < 0.01-0.05). After correction for percent body fat, only HSL and C3 mRNA levels remained significantly different between groups (P < 0.05). Taken together, these results suggest that aging has an effect on the up-regulation of HSL and C3 mRNA levels, whereas PPAR gamma expression seems to be related mainly to increased adiposity.

Leptin receptor Gln223Arg variant is associated with a cluster of metabolic abnormalities in response to long-term overfeeding.

OBJECTIVES: The role of the leptin receptor (LEPR) gene Gln223Arg polymorphism on the metabolic and body composition changes in response to overfeeding was studied. SUBJECTS: Twelve pairs of male monozygotic twins ate a 4.2 MJ day-1 energy surplus, 6 days week-1, during a period of 100 days. RESULTS: Overfeeding induced a significantly greater increase in glucose (P = 0.001 for percentage change) and insulin (P = 0.038) areas under the curve during oral glucose tolerance tests (OGTTs) in the GlnGln (n = 10) than in the GlnArg/ArgArg (n = 14) subjects. In addition, the GlnGln genotype was associated with a greater increase in plasma levels of leptin (P = 0.037) and total triglycerides (P = 0.003), as well as a greater decrease in high-density lipoprotein cholesterol (P = 0.010), than for the combined GlnArg/ArgArg genotypes. Body composition changes were not different between the genotypes. CONCLUSIONS: We conclude that the GlnGln subjects of the LEPR gene polymorphism are more susceptible to metabolic abnormalities when they are exposed to long-term positive energy balance. These findings provide new information on the genetic basis of individual differences in response to chronically elevated food intake.

Hypertriglyceridemic waist: A marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men?

BACKGROUND: The present study tested the hypothesis that simple variables, such as waist circumference and fasting plasma triglyceride (TG) concentrations, could be used as screening tools for the identification of men characterized by a metabolic triad of nontraditional risk factors (elevated insulin and apolipoprotein [apo] B and small, dense LDL particles). METHODS AND RESULTS: Results of the metabolic study (study 1) conducted on 185 healthy men indicate that a large proportion (>80%) of men with waist circumference values >/=90 cm and with elevated TG levels (>/=2.0 mmol/L) were characterized by the atherogenic metabolic triad. Validation of the model in an angiographic study (study 2) on a sample of 287 men with and without coronary artery disease (CAD) revealed that only men with both elevated waist and TG levels were at increased risk of CAD (odds ratio of 3.6, P<0.03) compared with men with low waist and TG levels. CONCLUSIONS: It is suggested that the simultaneous measurement and interpretation of waist circumference and fasting TG could be used as inexpensive screening tools to identify men characterized by the atherogenic metabolic triad (hyperinsulinemia, elevated apo B, small, dense LDL) and at high risk for CAD.

Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia.

OBJECTIVES: To investigate the relationships of fat cell weight (FCW) as well as of estimated total adipose cell number to fasting plasma leptin concentration. DESIGN: Cross-sectional correlational study. SUBJECTS: A sample of 63 men (mean age+/-s.d.: 36+/-4 y) and 42 premenopausal women (35+/-5 y). MEASUREMENTS: Adipose tissue (AT) biopsies were obtained in order to determine FCW as well as estimated adipose cell number. Fasting plasma leptin and insulin concentrations as well as various fatness and body fat distribution variables (underwater weighing and computed tomography) were also measured. RESULTS: In both genders, mean FCW as well as the estimated adipose cell number were significantly correlated with body fatness and AT distribution variables (0.41

Adipose tissue metabolism in young and middle-aged men after control for total body fatness.

The aim of this study was to compare the sc adipose tissue metabolism of young (29 +/- 4 yr) vs. middle-aged men (57 +/- 5 yr), once the concomitant variation in total adiposity was taken into account. For this purpose, sc abdominal and femoral adipose tissue lipoprotein lipase activities, as well as fat cell lipolytic responses, were investigated in 2 groups of 16 men, differing in age but displaying similar adipose tissue mass (within 2 kg) and sc abdominal adipose tissue area, measured by computed tomography (within 15 cm2). No difference was observed in adipose tissue lipoprotein lipase activity of young vs. middle-aged subjects, regardless of the adipose region considered. Epinephrine induced antilipolysis at low concentrations (10(-9) to 10(-7) mol/L) and a net lipolytic response at higher doses (10(-6) to 10(-5) mol/L), regardless of the subjects' age and the anatomic location of fat. In addition, the selective alpha2-adrenergic agonist, UK-14304, promoted a similar antilipolytic response in sc abdominal and femoral adipose cells from both groups. However, maximal lipolysis induced by isoproterenol (beta-adrenergic agonist) or by postadrenoceptor agents such as dibutyryl-cAMP, forskolin, and theophylline were lower in both adipose regions of middle-aged (as compared with young) men. No difference in the beta- or the alpha2-adrenoceptor sensitivity of sc adipose cells was observed between groups. These results indicate that there is, with age, a selective decrease in the lipolytic capacity to beta-adrenergic agonist, which seems to be caused by postadrenoceptor impairments. Because subjects in the 2 age-groups displayed similar body fatness, these alterations are independent from the age-expected increase in total adiposity.

Body fat distribution, the menopause transition, and hormone replacement therapy.

Endocrine changes resulting from the menopause transition dramatically modify women's hormonal milieu. The consequences of these changes not only lead to cessation of reproduction and accompanying symptoms in women, but also dramatically impact long-term health. Loss of estrogen has been associated with the development of cardiovascular disease. Central distribution and accumulation of adipose tissue, and the concomitant insulin resistant dyslipidemic state have emerged as important components of a cluster of metabolic abnormalities that are strongly related to coronary heart disease. Thus, estrogen deficiency may affect cardiovascular disease risk by mediating changes in body fat distribution. This article is an update of the literature in the area of menopause, hormone replacement therapy, and body fat distribution. Cross-sectional studies using anthropometric measurements of abdominal fat distribution most often failed to detect an effect of the menopause transition that was independent of advancing age and degree of obesity. The use of radiologic techniques such as DEXA and computed tomography, however, led to the conclusion that the menopause transition accelerates the selective deposition of intra-abdominal fat. Available longitudinal data also support an increase in central body fatness occurring with menopause. Most intervention trials on hormone replacement therapy and body fat distribution showed that the treatment prevented the increase in central adiposity that was noted in postmenopausal women receiving no treatment or placebo. These results are supported by retrospective studies that showed a lower WHR in hormone users vs non-users. Mechanisms potentially explaining the menopause-related acceleration in abdominal fat accumulation include changes in regional adipose tissue metabolism in the face of a positive energy imbalance. As some inconsistencies were found among studies, further investigations using longitudinal and intervention designs, as well as more precise methodologies to measure body fat distribution, are needed to clearly establish the effects of menopause and hormone replacement on abdominal body fat distribution and the concomitant increase in cardiovascular disease risk.