ApoB-100 gene EcoRI polymorphism. Relations to plasma lipoprotein changes associated with abdominal visceral obesity.

The aim of this study was to investigate whether the EcoRI restriction fragment length polymorphism (RFLP) of the apolipoprotein (apo) B-100 gene influences the associations described among obesity, regional adipose tissue distribution, and plasma lipoprotein levels. For this purpose, blood samples were collected from 56 healthy men for whom we had extensive measurements of regional adipose tissue distribution (both anthropometric and computed tomography-derived measurements) and data on the plasma lipoprotein-lipid profile. DNA was extracted from white blood cells, and RFLP analysis was performed. Subjects were classified into two groups on the basis of their apoB-100 EcoRI genotype: subjects homozygous for the major 11-kb allele, the 11/11 group (n = 40), and subjects carrying the minor 13-kb allele, the 13/11 group (n = 16). Subjects carrying the 13-kb allele had lower percent body fat and abdominal adipose tissue accumulation than subjects homozygous for the 11-kb allele (P < .05). Although leaner, the 13/11 group did not show a more favorable plasma lipoprotein-lipid profile than the group homozygous for the 11-kb allele. In fact, after statistical control for the difference in percent body fat between the two genotype groups, the 13/11 group showed significantly higher plasma cholesterol levels (P < .05) and nearly significantly higher apoB levels than the 11/11 group (P = .06). The association patterns between indices of regional adiposity and plasma cholesterol and apoB levels were also different between the two EcoRI genotype groups. Only in the 13/11 group was the abdominal visceral adipose tissue area significantly associated with these plasma variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women.

The amount of abdominal visceral adipose tissue measured by computed tomography is a critical correlate of the potentially "atherogenic" metabolic disturbances associated with abdominal obesity. In this study conducted in samples of 81 men and 70 women, data are presented on the anthropometric correlates of abdominal visceral adipose tissue accumulation and related cardiovascular disease risk factors (triglyceride and high-density lipoprotein cholesterol levels, fasting and postglucose insulin and glucose levels). Results indicate that the waist circumference and the abdominal sagittal diameter are better correlates of abdominal visceral adipose tissue accumulation than the commonly used waist-to-hip ratio (WHR). In women, the waist circumference and the abdominal sagittal diameter also appeared more closely related to the metabolic variables than the WHR. When the samples were divided into quintiles of waist circumference, WHR or abdominal sagittal diameter, it was noted that increasing values of waist circumference and abdominal sagittal diameter were more consistently associated with increases in fasting and postglucose insulin levels than increasing values of WHR, especially in women. These findings suggest that the waist circumference or the abdominal sagittal diameter, rather than the WHR, should be used as indexes of abdominal visceral adipose tissue deposition and in the assessment of cardiovascular risk. It is suggested from these data that waist circumference values above approximately 100 cm, or abdominal sagittal diameter values > 25 cm are most likely to be associated with potentially "atherogenic" metabolic disturbances.

Apolipoprotein E polymorphism modifies relation of hyperinsulinemia to hypertriglyceridemia.

The effect of apolipoprotein E polymorphism on the established relationships between glucose tolerance, plasma insulin levels, and plasma lipoprotein concentrations were investigated in a sample of women defined on the basis of apolipoprotein E phenotypes. In women with the apolipoprotein E epsilon 2 allele (n = 22), fasting plasma insulin and glucose and insulin areas under the curve measured during an oral glucose tolerance test were positively correlated with plasma triglyceride levels (0.48 < or = r < or = 0.70; P < 0.05). In this group, very-low-density lipoprotein cholesterol and very-low-density lipoprotein triglyceride concentrations were positively correlated with fasting insulin levels, the insulin area, and with the ratio of insulin area to glucose area. In women (n = 24) homozygous for the apolipoprotein E epsilon 3 allele (the most common allele), essentially similar associations were found. In contrast, in women (n = 17) with the apolipoprotein E epsilon 4 allele, no association was found between glucose tolerance, fasting and postglucose plasma insulin levels, and plasma lipid and lipoprotein levels. These results suggest that apolipoprotein E polymorphism substantially modifies the associations between glucose tolerance, plasma insulin levels, and plasma lipoprotein concentrations. Additional analysis of the data revealed that apolipoprotein E polymorphism did not alter the relationships between body fat distribution and fasting insulin and postglucose insulin levels, but no correlation was observed between fatness indexes and glucose tolerance among apolipoprotein E epsilon 2 carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic heterogeneity associated with high plasma triglyceride or low HDL cholesterol levels in men.

To further understand the factors involved in the regulation of high plasma triglyceride (TG) or low plasma high density lipoprotein cholesterol (HDL-C) levels, three groups of male subjects (normal TG with low HDL-C levels, high TG with normal HDL-C levels, and high TG with low HDL-C levels) were compared with a sample of normolipemic men with normal TG and HDL-C plasma levels. Mean age was 34 years (range, 20-42 years), and none of the subjects had plasma TG levels > 4.0 mmol/l or familial hypercholesterolemia. Both groups of subjects with high TG levels had a higher body mass index, waist circumference, waist-to-hip circumferences ratio, and a higher ratio of abdominal to femoral adipose tissue areas as measured by computed tomography when compared with normolipemic control subjects. However, during an oral glucose tolerance test only high TG-low HDL-C men had fasting hyperinsulinemia and higher plasma insulin levels compared with normolipemic subjects. In addition, the high TG-low HDL-C group showed reduced HDL apoprotein (apo) A-I levels and a low HDL2-C/HDL3-C ratio. These changes were observed along with a nonsignificant trend for a lower plasma postheparin lipoprotein lipase activity. However, among subjects with high TG and normal HDL-C levels, no evidence of insulin resistance or of a reduction in postheparin lipoprotein lipase activity was observed, suggesting that the high plasma TG levels could be attributed to an increased production of apo B-containing lipoproteins, as high plasma apo B and low density lipoprotein (LDL)-apo B levels were observed in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Is body fat loss a determinant factor in the improvement of carbohydrate and lipid metabolism following aerobic exercise training in obese women?

Thirty-one obese, premenopausal women aged 35.4 +/- 5.1 (SD) years exercised for 90 minutes at approximately 55% of maximal aerobic power (VO2max) four to five times a week for a period of 6 months. The training program induced a significant increase in VO2max (P < .001) and significant improvements in carbohydrate and lipid metabolism, as reflected by decreased plasma insulin (INS) concentrations measured in the fasting state and after glucose (GLU) ingestion (INS area, P < .001), by reduced plasma cholesterol (C) and low-density lipoprotein cholesterol (LDL-C) levels (P < .001), and by increased ratios of high-density lipoprotein cholesterol (HDL-C)/LDL-C and HDL2-C/HDL3-C (P < .05 and P < .001, respectively). Changes in body fat mass were positively associated with changes in the INS area/GLU area ratio (r = .49, P < .05) and with changes in very-low-density lipoprotein triglycerides ([VLDL-TG] r = .49, P < .05). Furthermore, changes in the INS area were positively associated with changes in VLDL-TG (r = .51, P < .05). Although no significant mean change in body composition was observed, important individual variation was noted. Twenty women showed a reduction in body fat mass (mean reduction, 2.63 +/- 2.2 kg), whereas 11 women showed an increase in adipose mass (mean increase, 2.79 +/- 2.36 kg). Comparable increases in VO2max were observed between the two groups. The group that showed a decrease in body fat mass with exercise also had significant improvements in carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels.

The relations of regional adipose tissue (AT) distribution measured by computed tomography (CT) to plasma insulin-glucose homeostasis and lipoprotein-lipid levels were studied in 58 obese and 29 lean control men. In the group of obese men, the visceral AT area measured by CT was positively correlated with fasting plasma triglyceride and insulin levels and with glucose and insulin areas under the curves measured during a 75-g oral glucose tolerance test. Visceral AT area was also negatively associated with plasma high-density lipoprotein (HDL) and HDL2 cholesterol levels. The relative accumulation of abdominal fat, estimated by the ratio of abdominal to femoral AT areas obtained by CT, was also a significant correlate of indices of carbohydrate metabolism and was the best univariate correlate of plasma lipoprotein levels. No significant associations were observed between the visceral AT area, the ratio of abdominal to femoral AT areas, and indices of carbohydrate and lipoprotein metabolism in the group of lean men. On the other hand, the subcutaneous abdominal AT area was a significant correlate of the glucose area under the curve in both groups of men, but this association was not independent from the percentage of total body fat. No relationship was observed between the femoral AT area and indices of carbohydrate metabolism in either lean or obese groups. In obese men, however, the femoral AT area was negatively correlated with plasma triglyceride concentration and positively correlated with plasma HDL and HDL2 cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Normalization of the metabolic profile in obese women by exercise and a low fat diet.

This study was performed to evaluate the additive effect of exercise and a low fat diet on body weight, body composition, and the metabolic profile in four obese women who were previously exercise-trained for 15 months. This study therefore included regular aerobic exercise for 15 months and a low fat diet plus exercise for an additional period of 14 months. After 15 months, mean body weight and fat losses corresponded to 6.4 and 8.4 kg, respectively. Significant reductions (P less than 0.05) in plasma insulin, cholesterol, apo B, and LDL-C were also observed. Following the second part of the study, mean cumulative body weight and fat losses were 11.0 and 11.3 kg, respectively. At this time, the subjects were still overweight, but their plasma glucose and insulin during an oral glucose tolerance test were essentially similar to values obtained in a sample of 22 nonobese women. With the exception of plasma apo B and HDL-C levels, plasma lipid and lipoprotein levels were also comparable to those observed in nonobese controls. These results thus indicate that aerobic exercise-training and a low fat diet can normalize the metabolic profile of obese women, even if their adiposity remains higher than that of lean women.

Regional variation in adipose tissue lipolysis in lean and obese men.

Biopsies of adipose tissue were obtained from two subcutaneous regions (abdominal and femoral) in a sample of 54 men (32 obese and 22 lean subjects). Clonidine-induced antilipolysis in femoral adipose cells was similar in both groups, whereas subcutaneous abdominal adipocytes of obese individuals showed a higher alpha 2-adrenergic response than did subcutaneous abdominal adipose cells from lean subjects. In addition, epinephrine had a biphasic effect in subcutaneous abdominal adipocytes from obese individuals, as it induced antilipolysis at low concentrations, and a net lipolytic response at higher doses. In contrast, the physiological amine promoted lipolysis in subcutaneous abdominal adipose cells of lean subjects. Epinephrine- and clonidine-induced antilipolysis of subcutaneous abdominal adipocytes was positively associated with the level of subcutaneous abdominal fat measured by computed tomography (CT). Finally, men with a high alpha 2-adrenergic response of subcutaneous abdominal fat cells were fatter than those with a low alpha 2-adrenergic component. These results suggest that, in men with a wide range of body fatness, variations in the lipolytic response of subcutaneous abdominal adipose cells to epinephrine appear to involve changes in the functional balance between alpha 2- and beta-adrenoceptors.

Estimation of deep abdominal adipose-tissue accumulation from simple anthropometric measurements in men.

Equations have been developed for the prediction of deep abdominal adipose-tissue (AT) accumulation from anthropometric measurements in a sample of 110 men. An equation including the waist circumference and age could predict 74% of the variance in the amount of deep abdominal AT with an SEE of 29.6 cm2 (29.2% of the mean deep abdominal AT value), whereas another equation including the sagittal diameter, the waist-to-hip ratio (WHR), and age explained 76.6% of its variance with an SEE of 28.1 cm2 (27.7%). Equations excluding age as an independent variable were also developed. These results indicate that equations in which simple anthropometric measurements are used can provide further information in the assessment of the risk of cardiovascular disease in men. However, we must remember that our ability to predict the amount of deep abdominal AT from anthropometry is limited.

Loss of abdominal fat and metabolic response to exercise training in obese women.

Numerous studies have shown that a high accumulation of abdominal fat is associated with metabolic complications and with an increased risk of coronary heart disease. The present study examined the effects of changes in body fatness and in the level of abdominal fat on metabolic variables in a sample of 13 obese premenopausal women, aged 38.8 +/- 5.3 (SD) yr. Women exercised for 90 min at approximately 55% of maximal aerobic power (VO2 max) four to five times a week for a period of 14 mo. The training program induced a significant increase in VO2 max and a mean reduction in body fat mass of 4.6 kg (P less than 0.01), with no change in fat-free mass. Measurement of adipose tissue areas by computed tomography indicated a greater loss of abdominal fat compared with midthigh adipose tissue (P less than 0.05). The training program also produced significant reductions in the insulinogenic index measured during an oral glucose tolerance test and in plasma cholesterol (Chol), low-density lipoprotein (LDL)-Chol, and apolipoprotein (apo) B levels (P less than 0.05). Training also significantly increased plasma high-density lipoprotein (HDL)-apo A-I and HDL2-Chol levels and decreased plasma HDL3-Chol concentration (P less than 0.05). Whereas no change in postheparin plasma lipoprotein lipase activity was noted, a significant decrease in postheparin plasma hepatic triglyceride lipase activity was observed after training (P less than 0.005). Metabolic responses were not correlated with changes in VO2 max but were significantly correlated with the reduction in body fat mass and/or with the loss of deep abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional variation in adipose tissue lipoprotein lipase activity: association with plasma high density lipoprotein levels.

The associations of adipose tissue lipoprotien lipase (AT-LPL) activity with body fatness and plasma lipoprotein levels were studied in the light of the recently described regional differences in AT-LPL activity. In this regard, heparin-releasable LPL activity was measured in abdominal and femoral adipose tissues of 29 pre-menopausal women. Body fatness variables were all positively correlated with abdominal and femoral AT-LPL activities expressed per 10(6) cells. However, abdominal and femoral AT-LPL activities expressed per unit of cell surface displayed divergent association patterns with body fatness and plasma lipoprotein levels. Indeed, only abdominal AT-LPL activity remained significantly correlated with body fatness variables after adjustment for fat cell surface. Furthermore, whereas abdominal AT-LPL activity tended to be negatively correlated with plasma HDL-cholesterol levels, femoral AT-LPL activity was positively correlated with plasma HDL2-cholesterol (r = 0.40, P less than 0.05) concentration and with the HDL2-cholesterol/HDL3-cholesterol ratio (r = 0.49, P less than 0.01). These results demonstrate the importance of taking into account the regional variation in metabolic activity of adipose tissue when studying its associations with body fatness, and with plasma lipoprotein levels. The lack of association between abdominal AT-LPL activity and plasma HDL2-cholesterol levels lead us to suggest that AT-LPL activity may not be causally related with plasma HDL levels.

Apolipoprotein E polymorphism alters the association between body fatness and plasma lipoproteins in women.

The aim of the present study was to investigate the associations between total adiposity, body fat distribution, and plasma lipoprotein levels within groups of women defined on the basis of apolipoprotein E phenotypes, in order to verify whether apoE polymorphism could modify these associations. In women having only apolipoprotein E3 isoforms (n = 24), body fat mass, the waist: hip circumference ratio, and computed tomography-derived total and intra-abdominal fat areas were all positively correlated with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) lipids and apolipoprotein B concentrations. These body fatness variables were also negatively correlated with plasma high density lipoprotein (HDL) cholesterol concentration. These associations were, however, altered in the groups of women carrying either apoE2 or E4 isoforms. Indeed, in women carrying the apoE2 isoform (n = 22), body fatness variables were predominantly associated with VLDL components concentration (0.05 greater than P less than 0.01) and with LDL triglyceride content. No association was found between adiposity and LDL cholesterol or apolipoprotein B levels in these women. In contrast, no relationship was found between total adiposity, regional fat accumulation, and VLDL fraction in women carrying the apolipoprotein E4 isoform (n = 17). In this latter group, computed tomography-measured total abdominal fat accumulation was positively correlated with LDL apolipoprotein B (r = 0.58, P less than 0.05) concentration, whereas intra-abdominal fat accumulation was positively correlated with both LDL cholesterol and apolipoprotein B concentrations (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Correlates of plasma very-low-density lipoprotein concentration and composition in premenopausal women.

Potential correlates of plasma very-low-density lipoprotein (VLDL) concentration and composition were studied in a sample of 75 premenopausal women. Fasting plasma free fatty acid (FFA) levels, as well as plasma glucose and insulin levels in the fasting state and during an oral glucose tolerance test, displayed significant positive correlations with plasma triglyceride (TG) and VLDL-TG levels (P less than .005). Plasma post-heparin lipoprotein lipase (LPL) activity, measured in a subsample of 31 women from the original sample, was negatively correlated with plasma TG, VLDL-cholesterol (CHOL), VLDL-TG, and VLDL-apolipoprotein (apo) B concentrations (.005 greater than P less than .05). Multivariate analyses showed that, after LPL was considered, the insulin area was the only other metabolic variable studied that was significantly correlated with VLDL-apo B concentration, whereas fasting FFA levels were significantly correlated with plasma TG and VLDL-TG levels. ANOVA revealed that plasma VLDL-CHOL, VLDL-TG, and VLDL-apo B levels were not associated with the glucose area, but were significantly associated with the insulin area (P less than .005). When the effect of insulin area was controlled for, the plasma FFA levels did not contribute significantly to the variance in VLDL-CHOL and VLDL-apo B, but showed an independent effect on VLDL-TG levels (P less than .05). Finally, stepwise multiple regression analyses indicated that once the variance explained by plasma LPL activity and by the insulin area was considered, no other metabolic variable could account for the variation in VLDL-CHOL and VLDL-apo B levels, whereas fasting FFA levels explained a further 5% of the VLDL-TG variance and one third of the variance observed in the VLDL-TG/apo B ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Associations between regional body fat distribution, fasting plasma free fatty acid levels and glucose tolerance in premenopausal women.

The associations between total adiposity, body fat distribution measured by computed tomography (CT) and estimated by the waist-to-hip ratio (WHR), regional fat cell morphology, fasting plasma free fatty acid (FFA) levels and glucose tolerance were studied in a sample of 37 premenopausal women aged 35.3 +/- 4.6 years (mean +/- s.d.). Body fat mass, CT-derived abdominal and femoral fat areas, as well as the abdominal fat cell weight were all significantly associated with fasting plasma FFA levels (0.34 less than r less than 0.49, 0.005 less than P less than 0.05), and with the glucose and insulin areas during the oral glucose tolerance test (OGTT) (0.36 less than r less than 0.70, 0.0001 less than P less than 0.05). No associations were found between the WHR, the femoral fat cell weight and fasting plasma FFA levels or glucose area during the OGTT. However, the WHR and the femoral fat cell weight were positively associated with insulin area. Plasma FFA levels were positively correlated with the glucose area during the OGTT, whereas no association was found between plasma FFA levels and the insulin area. Covariance analysis indicated that this effect of plasma FFA levels on the magnitude of glucose response to OGTT was independent from that of total adiposity or regional body fat distribution variables. These results emphasize the importance of plasma FFA levels as a correlate of glucose tolerance and suggest that the associations previously reported between obesity, regional body fat distribution, fat cell size and glucose tolerance are, at least partly, mediated by variations in plasma FFA levels.

Computed tomography-measured trunk fat and plasma lipoprotein levels in nonobese women.

The associations between total adiposity, adipose tissue distribution measured by computed axial tomography (CAT), regional variation in fat cell size, and plasma lipoprotein levels were studied in a sample of 22 premenopausal healthy nonobese women aged 34.6 +/- 3.1 years (mean +/- SD) (% body fat, 27.8 +/- 5.8). In these nonobese women, no associations were found between total adiposity, adipose tissue distribution, and plasma triglyceride or very-low-density lipoprotein levels. However, total adiposity (as reflected by the body density-derived fat mass and by the adipose tissue volume measured by CAT), as well as the total trunk fat areas (measured at the abdominal and thoracic levels) were positively correlated with plasma low-density lipoprotein (LDL) cholesterol (.05 greater than P less than .01) and LDL apolipoprotein (apo) B (.05 greater than P less than .0005) levels. Because of these associations with LDL-C and LDL apo B levels, these body fatness indicators were negatively correlated with the HDL-cholesterol/LDL-cholesterol and HDL-apo A-I/LDL-apo B ratios. However, few significant associations were observed between the proportion of abdominal fat estimated by the waist/hip circumference ratio (WHR) and the lipoprotein-lipid profile (r = .45 and r = .44, P less than .05 with HDL triglyceride (TG) and LDL-apo B/LDL-cholesterol ratio, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)