Increase in plasma pollutant levels in response to weight loss in humans is related to in vitro subcutaneous adipocyte basal lipolysis.

OBJECTIVE: To examine whether weight loss-induced changes in in vitro basal lipolysis of subcutaneous abdominal and femoral fat cells were related to those in plasma organochlorine levels. DESIGN: A 15 week weight loss program induced by a moderate caloric restriction. SUBJECTS: Seventeen men and 20 women (age 36-50 y, body fat 25-50%). MEASUREMENTS: In vitro basal lipolysis of subcutaneous abdominal and femoral adipocytes and plasma levels of five polychlorinated biphenyl congeners (Aroclor 1260, PCBs 118, 138, 153 and 180) and three chlorinated pesticides (dichlorodiphenyl dichloroethene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH) and hexachlorobenzene (HCB)) were measured before and after the weight reducing program. RESULTS: Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean+/-s.d., 9.4+/-4.1 vs 5.9+/-5 kg, respectively, P<0.05). Mean basal fat cell lipolysis did not vary before and after weight reduction, regardless of depots and genders. In response to weight loss, significant increases of all organochlorines investigated were observed in men, whereas only p,p'-DDE, Aroclor 1260, PCBs 153 and 180 significantly rose in women. In men, higher the increase in basal lipolysis of subcutaneous abdominal or femoral adipocytes, greater the rise in plasma levels of most pollutants (HCB, Aroclor 1260, PCBs 118, 138 and 153) was in response to weight loss (0.51相似文献   

Fasting insulin levels influence plasma leptin levels independently from the contribution of adiposity: evidence from both a cross-sectional and an intervention study

The aim of the present investigation was to determine whether leptinemia is only a reflection of the status of fat stores or if insulinemia has a significant influence over leptin levels. Study 1 focused on the association between fasting plasma insulin and leptin in subjects of the Quebec Family Study who were first classified as either high- or low-insulin individuals and were then individually matched on the basis of fat mass (FM). In Study 2, 19 men and 23 women took part in a 15-week weight loss program that consisted of drug therapy (fenfluramine, 60 mg/day) or placebo coupled to an energy-restricted diet (-2930 kJ/day). Body weight, FM, and fat-free mass (assessed by underwater weighing) as well as visceral and sc abdominal and mid-thigh adipose tissue measured by computed tomography were assessed before and after weight loss. Blood samples were drawn and analyzed for fasting plasma insulin and leptin before and after weight loss. In Study 1, significant positive associations were noted between log10 transformed fasting insulin and leptin in both men (r = 0.55, P < 0.0001) and women (r = 0.48, P < 0.0001). Moreover, after having carefully matched high-insulin to low-insulin individuals on the basis of FM, significantly lower leptin levels were observed in the low-insulin groups, in men (5.5 vs. 8.1 ng/mL, P < 0.05) as well as in women (18.7 vs. 24 ng/mL, P < 0.05). Results from Study 2 showed significant reductions of body weight, FM, fat-free mass, visceral abdominal tissue, sc abdominal tissue, and mid-thigh adipose tissue levels in men and women in response to the weight loss protocol. Moreover, the decrease in fasting plasma insulin was the only significant correlate of changes in fasting plasma leptin levels during weight loss, even after corrections for changes in FM in both men (r = 0.50, P < 0.05) and women (r = 0.46, P < 0.05). These results suggest that in a population characterized by a wide range of adiposity hyperinsulinemia has the potential to modulate leptin levels beyond what can be explained by total adiposity. Moreover, this relation also seems to exist in a dynamic setting (i.e. during weight loss) because changes in insulin were independent predictors of the changes in leptinemia in both men and women after correction for changes in FM.     

Effect of a moderate weight loss on adipose tissue lipoprotein lipase activity and expression: existence of sexual variation and regional differences.

OBJECTIVE: To evaluate the impact of moderate body weight loss on both adipose tissue lipoprotein lipase (AT-LPL) activity and expression and to verify whether variation in AT-LPL could be related to changes in lipid-lipoprotein metabolism. DESIGN: Intervention study of a 15-week weight reducing program (energy deficit: 500-800 kcal/d below the subjects' estimated sedentary energy expenditure). SUBJECTS: Thirty two obese subjects (14 men and 18 premenopausal women; aged 36-50 y) whose body fatness ranged from 34 to 54% fat. MEASUREMENTS: Adipose tissue biopsies from the abdominal and femoral depots, various fatness and fat distribution parameters (computed tomography and anthropometry), fasting plasma concentrations of high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides at baseline and 4-6 weeks after the 15-week weight reducing program, when subjects were weight stable. RESULTS: In response to weight loss, AT-LPL activity of both regions did not change in men, but decreased in women. Regarding AT-LPL expression, no interaction between time and sex was observed in response to the treatment. In both genders, the higher was the basal AT-LPL activity, the greater was the reduction of this enzyme activity in response to weight loss, in both the abdominal and femoral depots (-0.53相似文献   

Effects of oral contraceptives on glucoregulatory responses to exercise

Some of the effects of oral contraceptives (OCs) to alter glucoregulation may be ameliorated by exercise. To test this premise, the effects of acute aerobic exercise on postprandial glucose, insulin, and C-peptide responses (area under the curve [AUC]) were measured in 8 users of low-dose estrogen and progestin OCs (OC(+)) and 10 women not using OCs (OC(-)). They completed 2 randomly ordered intervention trials: (1) aerobic exercise on 3 consecutive days with a 2.5-hour, 75-g oral glucose tolerance test (OGTT) on day 4, and (2) no exercise for 3 days prior to the OGTT (control trial). The exercise was 50 minutes of treadmill walking at 70% (.-)VO(2max). The groups were similar in age (27 +/- 3 years), waist-to-hip ratio (0.74 +/- 0.01), and cardiorespiratory fitness (32.5 +/- 1.6 mL x kg body mass(-1) x min(-1)). Fasting plasma glucose, C-peptide, and insulin levels were similar (P >.05) between groups in the control trial. In both trials, glucose(AUC) was significantly greater (13%, P <.05) in OC(+). Exercise resulted in a significant (P <.05) decrease in fasting plasma glucose and insulin, insulin(AUC), glucose(AUC) x insulin(AUC), and C-peptide(AUC) in both groups, suggesting enhanced insulin action and/or reduced pancreatic insulin secretion. Hepatic insulin extraction ([C-peptide(AUC) - insulin(AUC)())]/C-peptide(AUC)) was increased following exercise only in OC(+). Thus, insulin action was enhanced in response to exercise in young sedentary women independent of OC use. The mechanisms for the acute exercise effect on insulin action may be different in OC users compared with normally menstruating women.     

Plasma levels of agouti-related protein are increased in obese men

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.     

Relationship of visceral adipose tissue to metabolic risk factors for coronary heart disease: is there a contribution of subcutaneous fat cell hypertrophy?

Visceral adipose tissue (VAT) accumulation is an important correlate of the metabolic complications found in obese patients. The aim of this study was to evaluate the respective contribution of VAT deposition versus subcutaneous abdominal or femoral fat cell hypertrophy as correlates of the metabolic risk profile in 69 men and 65 premenopausal women (aged 35+/-5 years) with a wide range of fatness (body mass index, 18 to 57 kg/m2). In both genders, VAT accumulation was positively correlated with fasting plasma insulin, triglyceride (TG), and low-density lipoprotein (LDL)-apolipoprotein B (apo B) levels and the cholesterol (CHOL)/high-density lipoprotein (HDL)-CHOL ratio (.24 < or = r < or = .71, P < .05). A similar pattern of positive relationships was found between subcutaneous abdominal fat cell weight and metabolic risk variables in men and women (.33 < or = r < or = .60, P < .01). Positive associations were also observed in women between femoral fat cell weight and fasting plasma insulin, TG, and CHOL levels and the CHOL/HDL-CHOL ratio (.29 < or = r < or = .42, P < .05). However, only plasma TG concentrations and the CHOL/HDL-CHOL ratio were positively correlated with femoral fat cell weight in men (r = .30, P < .05). To better investigate the relationships between the metabolic risk profile and hypertrophic subcutaneous obesity, individuals with small versus large subcutaneous abdominal adipocytes were matched according to VAT accumulation. Men with large abdominal fat cells displayed higher plasma TG and LDL-apo B levels compared with men characterized by small abdominal adipocytes (P < .05). Stepwise multiple regression analyses showed that subcutaneous abdominal fat cell weight was the best independent variable predicting plasma TG and LDL-apo B levels in men. No significant difference was found in the metabolic profile of subjects displaying small versus large femoral adipocytes. Taken together, these results suggest that for a given VAT deposition, the presence of hypertrophied subcutaneous abdominal adipocytes in men appears to be associated with further deterioration in the metabolic risk profile. On the other hand, the hypertrophy of femoral adipocytes does not further alter the metabolic complications generally related to obesity in both men and women.     

Appetite after weight loss by energy restriction and a low-fat diet-exercise follow-up

OBJECTIVE: The aim of the present study was to determine the impact of weight loss on appetite as measured by visual analog scale (VAS). METHODS: Seventeen subjects (10 men and seven women) took part in a 15 week weight loss program which consisted of drug therapy (fenfluramine 60 mg/day) or placebo coupled to an energy restriction (-2930 kJ/day; phase 1) followed by an 18 week low-fat diet-exercise follow-up (phase 2). Subjects were given a standardized breakfast before and after phase 1 as well as after phase 2. Individuals were asked to fill out VAS before and at 0, 10, 20, 30, 40, 50 and 60 min after this test meal. Blood samples were drawn before the meal and at 0, 30 and 60 min postprandially and analyzed for glucose and insulin. Fasting plasma cortisol and leptin were also determined. RESULTS: An increase in the fasting desire to eat, hunger and prospective food consumption (PFC) was observed after phase 1 and to an even greater extent after phase 2 in both men and women. In the fasting state, positive correlations were observed between changes in the desire to eat (r=0.76; P<0.05) as well as changes of PFC (r=0. 82; P<0.05) and changes in cortisol at the end of phase 1 for women. In response to phase 1, statistically significant correlations were found between changes of hunger (r=0.64; P<0.05) and desire to eat (r=0.67; P<0.05) as measured by AUC in response to the meal and changes of fasting plasma cortisol in men. The most consistent predictor of changes of baseline desire to eat (r=0.68 P<0.05), fullness (r=-0.78, P<0.05) and PFC (r=0.91, P<0.01) during phase 2 was the change in fasting cortisol in men. Changes of fullness were also associated with changes of fasting leptin in men (r=0.68; P<0. 05) during phase 2. CONCLUSION: These results suggest that weight loss is accompanied by an increase of baseline appetite in both men and women and that the most consistent predictor of these changes in appetite seems to be changes in fasting plasma cortisol.     

Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women

There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. We studied the effect of the association between circulating interleukin 6 (IL-6) levels, one of the major mediators of inflammation, and C-reactive protein on insulin resistance and blood pressure in 228 healthy volunteers. The plasma IL-6 concentration was significantly and similarly associated with systolic (SBP) and diastolic (DBP) blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI) in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r = 0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter associations persisted after controlling for body mass index (r = 0.15 and r = 0.19; P = 0.02 and P: = 0.0004 for SBP and DBP, respectively; r = 0.24 and r = 0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively). Gender and smoking status significantly influenced the results. Although IL-6 levels were significantly associated with fasting insulin and FIRI in men, these significant correlations were not observed in women. Conversely, although IL-6 levels were significantly associated with SBP and DBP in women, these coefficients were not statistically significant in men. All of these associations were lost among smokers and remained significant in nonsmokers. As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum CRP levels correlated significantly with IL-6 in all the subjects, but mainly in nonsmokers and men. Of note was that this significant relationship was lost among smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike IL-6, the associations between CRP and these parameters were similar in men and women and in smokers and nonsmokers. For insulin and FIRI they were stronger in women and in nonsmokers. CPR significantly correlated with the WHR only in men (r = 0.22; P = 0.01). Using multiple linear regression in a stepwise manner to predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03), but not fat mass or SBP, independently contributed to 11% of its variance in men. When CRP was introduced into the model, the latter (P < 0.0001) and smoking status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its variance. When CRP was introduced into the model, again only SBP (P = 0.01) contributed to 10% of the variance in IL-6 levels. In 25 of these subjects, insulin sensitivity was determined using the frequently sampled iv glucose tolerance test with minimal model analysis, and circulating IL-6 levels were strongly associated with the insulin sensitivity index (r = -0.65; P < 0.0001). Again, this relationship was even stronger in men (r = -0.75; P < 0.001) and was not significant in women (r = -0.26; P = NS). In all of these subjects, only insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the variance of IL-6 levels in a multiple linear regression analysis. In summary, circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitute a significant proatherogenic cytokine. The mechanisms of these associations should be further investigated.     

Plasma oestrone-fatty acid ester levels are correlated with body fat mass in humans

OBJECTIVE: The metabolites of steroidal hormones, including sulphate, glucuronide, and fatty acid (FA) ester derivatives, have received little attention, although these steroid derivatives are essential components in the global assessment of steroid metabolism. The study of FA-derivatives could, in obesity, contribute some insights into factors modulating steroid metabolism and their plasma levels. In a recent study we found that, in rats, an oestrone-fatty acid ester (E1-FA) was produced by white adipose tissue and released into lipoproteins in the blood-stream. We have examined whether E1-FA levels correlate with body fat and insulin sensitivity in humans. SUBJECTS: A sample of 20 men and 22 women with varying levels of total body fat (mean body mass index (BMI) 29.2 +/- 4.7, range 22.2-35.8 in men; mean BMI 27.6 +/- 6.3, range 16.8-37.9 in women). All participants were healthy. MEASUREMENTS: We measured oestrone fatty acid esters (E1-FA), body fatness, and body fat distribution variables, as well as insulin sensitivity through a frequently sampled intravenous glucose tolerance test. Plasma E1-FA and serum leptin levels were measured by radioimmunoassay. RESULTS: E1-FA levels strongly correlated with BMI (r = 0.69, P = 0.001 in men; r = 0.75, P < 0.0001, in women) percent body fat (PBF, r = 0.52. P = 0.018 in men; and r = 0.69, P < 0.0001, in women) and with the sum of 4 fat skinfolds (sigma skinfolds). E1-FA level was significantly and positively associated with fasting insulin (r = 0.62, P = 0.003 in men, and r = 0.48, P = 0.023 in women) but not with fasting glucose levels. E1-FA correlated with insulin sensitivity (SI, r = -0.72 in men; and -0.76, in women, both P < 0.0001). In men, E1-FA levels also correlated with systolic blood pressure (r = 0.59, P = 0.01), total triglycerides (r = 0.63, P = 0.003), VLDL-triglycerides (r = 0.62, P = 0.004) and VLDL-cholesterol (r = 0.48, P = 0.03), but not with diastolic blood pressure, serum total or LDL-cholesterol, or total and HDL2 and HDL3 subfractions of HDL cholesterol. After controlling for fat mass, only the correlation between VLDL-triglycerides and E1-FA levels remained significant. In women, E1-FA levels correlated with total triglycerides (r = 0.66, P = 0.001), VLDL-triglycerides (r = 0.65, P = 0.001), VLDL-cholesterol (r = 0.63, P = 0.002), LDL-cholesterol (r = 0.57, P = 0.005) and total and HDL2 and HDL3 subfractions of HDL cholesterol (r = -0.58, -0.48, -0.61, P = 0.004, 0.02 and 0.002, respectively), but not with systolic or diastolic blood pressure or total cholesterol. However, covariance analysis revealed that controlling for the concomitant variation in body fat mass eliminated all these associations. Fasting plasma E1-FA concentration correlated with serum leptin (r = 0.60, P = 0.005 in men; r = 0.75, P = 0.0001, in women). However, these correlations no longer persisted after controlling for fat mass (r = 0.33 and 0.36, P = NS). Stepwise regression analysis models were tested, with E1-FA as the dependent variable, and sigma skinfolds and SI as independent covariables. Both the sigma skinfolds (P = 0.03) and SI (P = 0.01) entered the equation at a statistically significant level in men. Therefore, insulin sensitivity was related to E1-FA independently of fat in men. In women only sigma skinfolds (P = 0.04) entered the regression model at a statistically significantly level. Fifty-seven percent of the variance in plasma E1-FA levels in men, and 50% in women, was accounted for using a regression model that combined these variables. CONCLUSIONS: Oestrone-fatty acid esters circulate in human blood in proportion to body fat, independently of gender. Plasma oestrone-fatty acid ester levels are associated with insulin sensitivity in men, independently of body fat. These findings may widen our perspective on the regulation of insulin action and control of body weight.     

The effect of physiologic hyperinsulinemia during an oral glucose tolerance test on the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in healthy young adults born with low and with normal birth weight

Several data support that adrenal hyperandrogenism affects women with low birth weight (LBW). We also found an association between serum dehydroepiandrosterone (DHEA) and fasting insulin levels. The aim of our study was to detect the acute effects of reactive hyperinsulinemia during oral glucose tolerance test (OGTT) on DHEA(S) levels in LBW men and women. Fifty three men and 47 women (of those, 37 men and 33 women were LBW) were enrolled. DHEA, DHEAS, and insulin levels were measured before and during OGTT. Cortisol was also measured. DHEA/cortisol ratio during OGTT was calculated to analyze the acute effect of hyperinsulinemia on DHEA levels. During OGTT, DHEA and cortisol levels decreased in each individual, independently of gender and birth weight. Serum DHEAS decreased to a minor (but significant) extent only in LBW women (p<0.05). The rate of DHEA/cortisol increased in both gender, independently of birth weight. The increase of the rate of DHEA/cortisol during OGTT was associated with maximal insulin response (r = 0.45, p<0.05) and with the insulin(AUC) (r = 0.48, p<0.05) in women. Our results suggest that reactive hyperinsulinemia during OGTT might activate the androgen pathway of adrenal cortex including DHEA production. Therefore acute hyperinsulinemia might counterbalance to some extent the diurnal decrease of DHEA during OGTT.     

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相似文献   

Post-heparin lipolytic enzyme activities, sex hormones and sex hormone-binding globulin (SHBG) in men and women: The HERITAGE Family Study

We tested the hypothesis that androgen, estrogen, and sex hormone-binding globulin (SHBG) levels would be significantly related to post-heparin hepatic lipase (HL) and lipoprotein lipase (LPL) activities in a sample of Caucasian men (n = 233) and women (n = 235) aged 17-64 years from the HERITAGE Family Study. Body composition (hydrostatic weighing), abdominal adipose tissue distribution (computed tomography), plasma lipid-lipoprotein and hormone levels, and post-heparin lipases activities were measured. HL activity was significantly higher in males, whereas LPL activity was higher in women (P < 0.005). In women only, HL activity was positively associated with body fat mass (r = 0.17, P < 0.05) and intra-abdominal adipose tissue area (r = 0.18, P < 0.05). Significant associations were also found between fasting insulin and LPL activity (r = -0.16, P < 0.05 and r = -0.18, P < 0.005) as well as HL activity (r = 0.22, P < 0.005, and r = 0.27, P < 0.0001) in men and women, respectively. A positive association between total testosterone and HL activity was noted in men (r = 0.13, P = 0.05). In women, plasma SHBG levels were negatively associated with HL activity (r = -0.48, P < 0.0001), and statistical adjustment for body fat mass, visceral adipose tissue area, and fasting insulin did not attenuate this correlation. In multivariate analyses with models including adiposity variables and measurements of the hormonal profile, insulin, and testosterone levels were both independent positive predictors of HL activity in men. In women, hormone use was a significant positive predictor, and SHBG level a strong negative predictor of HL activity, independent of plasma estradiol and testosterone concentrations. Fasting insulin was the only significant predictor of LPL activity in men (negative association), whereas menstrual status, fasting insulin (negative associations), and plasma SHBG levels (positive association) were all independent predictors of LPL activity in women. These results suggest that the postulated sensitivity of lipolytic enzymes to androgens and estrogens is reflected by a strong negative association between SHBG levels and HL, and a lower magnitude positive association of this hormonal parameter to LPL activity in women. These associations appear to be independent from concomitant variation in total adiposity or body fat distribution.     

Differences in mechanisms between weight loss-sensitive and -resistant blood pressure reduction in obese subjects.

This study was conducted to clarify the mechanisms involved in the sensitivity for blood pressure (BP) reduction in response to weight loss. In particular, we focused on the contributions of sympathetic nervous system activity and fasting plasma leptin and insulin levels to BP levels during weight loss in obese subjects with weight loss-sensitive and -resistant BP reduction. Sixty-one young, obese untreated hypertensive men (HT) and 52 obese normotensive men (NT) were enrolled in a weight loss program consisting of a low caloric diet and aerobic exercise over a 24-week period. At entry and at week 24, body mass index (BMI), BP, plasma norepinephrine (NE), leptin and insulin were measured. Successful weight loss and BP reduction were respectively defined as a more than a 10% reduction in BMI or mean BP from baseline at week 24. More than 60% of subjects in either group successfully achieved weight loss by this definition. The percentage of subjects who successfully achieved BP reduction was higher (64%) among those subjects who achieved weight loss than among those who did not (22%). Plasma NE level at entry in subjects who failed to achieve BP reduction despite weight loss was significantly higher than that in subjects who succeeded in BP reduction. Plasma leptin and insulin levels were similar between subjects with and without BP reduction. In addition, the absolute decrement and percent decrement in plasma NE in subjects who succeeded in BP reduction were significantly greater than those in subjects who failed to reduce their BP. Absolute and percent decrements in plasma leptin and insulin were similar in both groups. These results suggest that individuals who are resistant to weight loss-induced BP reduction have more sympathetic overactivity both at the outset of and during weight loss.     

The degree of hyperinsulinemia and impaired glucose tolerance predicts plasma leptin concentrations in women only: a new exploratory paradigm

Plasma leptin has been shown to correlate positively with many indices of obesity, as well as insulin resistance. For a given body weight, the levels are higher in women than in men, but the reasons for this difference are not clear. Insulin has been shown to stimulate leptin production by adipose tissue in vivo and in vitro. Previous studies have reported that leptin levels are similar in diabetic and nondiabetic individuals. However, these studies were not performed in newly diagnosed diabetics, and other variables (such as gender) could have confounded the results. Therefore, the goal of the present cross-sectional study is to examine the effect of metabolic variables (such as glucose and insulin) on plasma leptin concentrations in men and women separately. We measured leptin levels in 48 subjects (17 with newly diagnosed type 2 diabetes mellitus, 13 with impaired glucose tolerance [IGT], and 18 normal individuals). The 3 groups were well matched for gender, age, and body mass index (BMI). When adjusted for the BMI and gender, a statistically significant gender-related difference in mean plasma leptin was observed across the 3 glucose tolerance subgroups (P < .03 by analysis of covariance [ANCOVA]). More specifically, plasma leptin levels were, on average, 44% lower in women with diabetes or IGT versus normal women (P < .02). No such between-group difference was observed in the men. In univariate analysis in the same female subgroup, plasma leptin correlated positively with fasting insulin (rs = +.43, P < .06) and negatively with 2-hour post-75-g glucose load plasma glucose concentration (rs = -.54, P < .02). In a multiple regression model controlling for the BMI in the female subgroup, circulating insulin and glucose concentrations 2 hours after the 75-g glucose load were good predictors of fasting plasma leptin (r = +.38, P = .02 and r = -.70, P < .001, respectively). Leptin levels in women appear to be influenced independently and to an important degree by ambient plasma glucose and plasma insulin concentrations. These findings suggest that the synthesis of leptin by adipose tissue is more susceptible to in vivo regulation by insulin and glucose in women than in men. Plasma leptin concentrations were also lower in women with IGT or type 2 diabetes versus normal women, suggesting that fasting and/or postprandial hyperglycemia interferes with the stimulatory effect of plasma insulin on the synthesis of leptin by adipose tissue in women only.     

High plasma leptin concentrations in hypertensive men but not in hypertensive women.

OBJECTIVE: Previous studies on humans have reported higher leptin levels in women than in men, independent of body fat, and leptin has been correlated with insulin resistance in men but not in women. Since insulin resistance is thought to play a role in raising blood pressure, we investigated sex differences in leptin concentrations between hypertensive and normotensive individuals. METHODS: Ninety-two nondiabetic hypertensive patients (48 men and 44 women) and 92 age, body mass index (BMI)-matched normotensive control individuals were studied. Fasting plasma glucose, insulin, leptin and lipoprotein concentrations, glucose and insulin responses to 75 g oral glucose tolerance test (OGTT) and insulin suppression tests were determined. RESULTS: Fasting plasma leptin concentrations were higher in hypertensive men than in normotensive men (5.1 +/- 0.5 versus 3.9 +/- 0.4 ng/ml, P = 0.015). However, fasting plasma leptin concentrations were not significantly different between hypertensive and normotensive women (11.8 +/- 1.0 versus 10.9 +/- 1.0 ng/ml, P = 0.440). Fasting plasma leptin concentrations showed good correlation with BMI, body fat, fasting plasma insulin concentrations, and insulin area to OGTT in both men and women (all P < 0.001). However, fasting plasma leptin concentrations were related to steady-state plasma glucose (SSPG) concentrations, a measure of insulin sensitivity by insulin suppression test, in men only (P < 0.001). After adjustment for body fat amount, age and duration of hypertension, fasting plasma leptin levels still correlated significantly with SSPG concentrations in men. These four variables together accounted for a 67.9% variation in fasting plasma leptin levels in men. In women, body fat amount was the only significant determinant for plasma leptin levels. These four variables accounted for a 78.2% variation in plasma leptin levels in women. CONCLUSIONS: Our study confirmed a sex difference in leptin levels both in hypertensive and normotensive subjects. Higher plasma leptin concentrations in hypertensive men but not in hypertensive women when compared with normotensive control individuals was also demonstrated. These observations are consistent with the findings that plasma leptin is correlated with insulin sensitivity in men but not in women. Further studies are needed to understand the causes and consequences of sex effects on leptin in blood pressure regulation.     

Oxidative stress is associated with adiposity and insulin resistance in men

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2alpha (PGF2alpha) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2alpha than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2alpha were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2alpha and glucose infusion rate in obese men (r = -0.552; P < 0.05) and all men (r = -0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2alpha were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2alpha are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.     

Gender differences in relation to leptin concentration and insulin sensitivity in nondiabetic Chinese subjects.

OBJECTIVE: To investigate the relationship between fasting plasma leptin concentrations and insulin resistance in Chinese men and women. DESIGN: Cross-sectional study design. SUBJECTS: Ninety-six nondiabetic Chinese (51 men and 45 women) with body mass index (BMI) between 18.4-35.8 kg/m2 were studied. MEASUREMENTS: Plasma glucose and insulin concentrations were measured every 30 min for 2 h after a 75 g oral glucose load. The degree of insulin resistance was assessed using a modified insulin suppression test. Plasma leptin values were determined by radioimmunoassay. RESULTS: Fasting plasma glucose, glucose areas, fasting insulin, insulin areas, most of the lipoprotein concentrations and steady state plasma glucose (SSPG) concentrations were relatively similar between men and women. Despite the fact that men had higher BMI values (26.1 +/- 0.5 vs 24.7 +/- 0.5 kg/m2, P < 0.05), fasting plasma leptin concentrations were significantly lower in men than in women (4.9 +/- 0.5 vs 9.0 +/- 0.8 ng/ml, P < 0.001). Fasting leptin values were positively related to SSPG concentrations by simple correlation analysis in both sexes. However, this relationship persisted in men (r = 0.513, P < 0.01) but not in women (r = 0.119, P = NS) after adjustment for BMI. Multiple regression analysis showed that SSPG concentrations, BMI, glucose and insulin responses together accounted for 62.5% and 52.2% of the variation in plasma leptin concentrations in Chinese men and women respectively. CONCLUSION: Fasting plasma leptin concentrations were lower in Chinese men than in Chinese women despite the higher BMI observed in men. After adjustment for BMI, plasma leptin values correlated with the degree of insulin resistance in men but not in women.     

Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women

OBJECTIVE: The purpose of this study was to determine changes in adiponectin levels with moderate weight loss, weight loss plus aerobic exercise, or weight loss plus resistive exercise in overweight and obese, sedentary postmenopausal women. DESIGN: Longitudinal, clinical intervention study of 6-month (3 x /week) program of either weight loss (WL, n=15), weight loss + aerobic exercise (WL+AEX, n=16), or weight loss + resistive exercise (WL+RT, n=9) SUBJECTS: We studied 40 sedentary, overweight and obese (body mass index, BMI=32+/-1 kg/m(2), X+/-s.e.m.) postmenopausal (57+/-1y) women. MEASUREMENTS: Fat mass and fat-free mass (FFM) by dual-energy X-ray absorptiometry, plasma insulin, leptin, and adiponectin by radioimmunoassay. RESULTS: Age, body weight, BMI, waist and hip circumferences, waist-to-hip ratio, VO(2)max, percent fat, total body fat mass, FFM, and fasting plasma glucose, insulin, leptin, and adiponectin concentrations were similar among WL, WL+AEX, and WL+RT groups before the interventions. In all women combined, body weight, BMI, and waist and hip circumferences decreased (P < 0.001). There was a significant absolute decrease in percent body fat from 47 to 44%, representing a 13% decrease in total fat mass and a -1.6% change in FFM. Fasting concentrations of plasma adiponectin did not change (40+/-16%, P=NS), whereas fasting plasma glucose, insulin, and leptin all decreased (P<0.001). CONCLUSIONS: Plasma adiponectin levels do not change with a 6-month moderate weight reduction program even when accompanied by aerobic or resistive exercise training in overweight and obese postmenopausal women.     

Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding

Weight reduction after gastric bypass surgery has been attributed to a decrease of the orexigenic peptide ghrelin, which may be regulated by insulin and leptin. This study examined effects of long-term weight loss after laparoscopical adjustable gastric banding on plasma ghrelin and leptin concentrations and their relationship with insulin action. Severely obese patients (15 women, three men, 36 +/- 12 yr) underwent clinical examinations every 3 months and modified oral glucose tolerance tests to assess parameters of insulin sensitivity and secretion every 6 months. After surgery, body mass index fell from 45.3 +/- 5.3 to 37.2 +/- 5.3 and 33.6 +/- 5.5 kg/m(2) at 6 and 12 months, respectively (P < 0.0001). This was associated with lower (P < 0.0001) plasma glucose, insulin, insulin resistance, waist circumference, and blood pressure. Plasma leptin decreased from 27.6 +/- 9.5 to 17.7 +/- 9.8 (P = 0.0005) and 12.7 +/- 5.1 ng/ml (P < 0.0001). Plasma ghrelin was comparable before and at 6 months (234 +/- 53; 232 +/- 53 pmol/liter) but increased at 12 months (261 +/- 72 pmol/liter; P = 0.05 vs. 6 months). At 6 and 12 months, ghrelin levels correlated negatively with fasting plasma insulin levels and hepatic insulin extraction but not with body mass or insulin action.In conclusion, prolonged weight loss results in a rise of fasting ghrelin concentrations that correlates with fasting insulin concentrations but not improvement of insulin sensitivity.     

Independent effects of obesity and cortisol in predicting cardiovascular risk factors in men and women

OBJECTIVES: Recent data suggest that higher plasma cortisol may be associated with hypertension and insulin resistance in otherwise healthy men, as it is in Cushing's syndrome. However, obesity in women is associated with lower plasma cortisol concentrations. This study sought to establish whether plasma cortisol is associated with cardiovascular risk factors in women as it is in men, and whether these relationships in either sex are confounded by obesity. DESIGN: A population-based cross-sectional study. SETTING: The MONICA study in northern Sweden. SUBJECTS: From a target cohort of 2500, 1921 subjects took part and 226 were randomly selected because they attended between 07.00 and 09.00 h after an overnight fast. A 75 g oral glucose tolerance test was performed and blood sampled at baseline and 2 h after glucose. RESULTS: Plasma cortisol was lower in relatively obese subjects: in men, this was observed only in the 2 h sample (r = -0.23, P = 0.02) and in women only in the fasting sample (r = -0.26, P < 0.01). Simple regression analysis did not identify relationships between plasma cortisol and blood pressure, serum lipids, fasting insulin or glucose tolerance. However, after adjusting for the effect of obesity by multiple regression, higher plasma cortisol was independently associated with higher diastolic blood pressure in men (r = 0.21, P = 0.04) but not in women, and higher fasting serum triglyceride levels in women (r = 0.28, P < 0. 001) but not in men. CONCLUSIONS: Increasing obesity and plasma cortisol concentrations make independent and sex-specific contributions to variations in blood pressure and aspects of the insulin resistance syndrome. Adverse cardiovascular risk is greatest in those with the combination of obesity and failure to downregulate plasma cortisol levels.