Adiponectin is associated with bone mineral density in perimenopausal women.

The aim of the current investigation was to investigate any potential effect of fasting plasma adiponectin concentration on bone tissue, and to find possible relationships of fasting plasma adiponectin level with different body composition, insulin sensitivity and physical performance parameters in a group of healthy perimenopausal women. Twenty-one premenopausal and 17 early postmenopausal women participated in this study. The women were matched for body mass index (BMI) and level of mean daily energy expenditure. Women had similar adiponectin (8.4 +/- 3.9 vs. 9.9 +/- 5.4 microg/ml) and leptin values (12.0 +/- 7.7 vs. 14.0 +/- 8.2 ng/ml) before and after menopause. Significant relationships were observed between plasma adiponectin and bone mineral content, total bone mineral density (BMD) and lumbar spine BMD values (r > - 0.36; p < 0.05). Furthermore, adiponectin had a significant negative association with total BMD (beta = - 1.228; p = 0.004) and lumbar spine BMD (beta = - 0.312; p = 0.005) independent of the influence that other measured body compositional, hormonal or physical performance factors may exert on BMD. Adiponectin was also significantly related to waist-to-hip ratio (WHR) (beta = - 2.300; p = 0.002) and fasting insulin resistance index (FIRI) (beta = - 0.006; p = 0.007) in separate regression models. No relationship was observed between leptin and measured bone, physical performance and insulin resistance values. Leptin significantly correlated to BMI (beta = 0.018; p = 0.034), lean body mass (beta = 0.025; p = 0.024) and fat mass (beta = 0.019; p = 0.001) in separate regression models. In conclusion, the results of present study show that circulating adiponectin appears to exert an independent effect on BMD in perimenopausal women and may represent a link between adipose tissue and bone mineral density.     

Relationship of plasma leptin and adiponectin concentrations with menopausal status in Tunisian women

To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3 ± 7.6 years) and 180 postmenopausal women (mean age 53.4 ± 6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDL-cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre- to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance.     

Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-alpha, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 +/- 0.8 kg/m2; age, 57 +/- 1 yr). A subset of these women without diabetes (n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin (r = -0.46, P < 0.05) and tended to be negatively related to adiponectin (r = -0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression; fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-beta-actin ratio, 2.26 +/- 0.46 vs. 3.31 +/- 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.     

The relation of serum adiponectin and leptin levels to metabolic syndrome in women before and after the menopause

INTRODUCTION: It is well known that there is a higher prevalence of cardiovascular risk factors and metabolic syndrome (MS) in postmenopausal women. Recently it has become evident that adiponectin and leptin secreted by adipose tissue may be involved in the pathophysiology of MS. The aim of the study: was to assess the effects of the menopause on the relationships between adiponectin and leptin and different cardiovascular and metabolic risk factors. MATERIALS AND METHODS: A total of 56 postmenopausal women and 75 premenopausal subjects were enrolled in this study. We measured blood pressure, BMI, waist circumference and WHR, triglycerides (TG), high density lipoprotein cholesterol (cHDL) levels and fasting glucose and applied the oral glucose tolerance test (OGTT). Women were categorised as having 0, 1, 2, 3 or more risk factors. The presence of at least 3 abnormalities was defined as MS. Serum was assayed for adiponectin and leptin by the radioimmunoassay (RIA) method. RESULTS: A decline in adiponectin was related to an increased number of MS variables in postmenopausal and premenopausal women. Postmenopausal women with MS had significantly lower adiponectin concentrations than premenopausal women with MS. Serum adiponectin concentrations were inversely correlated to leptin in postmenopausal women. In premenopausal women no clear relationships were found between serum leptin and the number of metabolic disturbances. In contrast to young women, postmenopausal women showed an increase in leptin secretion with a growing number of MS elements. Compared to premenopausal women with MS, postmenopausal women with MS had higher levels of leptin. We found associations between leptin and different risk factors, mainly in the postmenopausal group. When the presence of MS was used as a dependent variable (yes/no) and adiponectin, leptin and menopause status as independent factors, adiponectin and leptin remained significant variables related to MS. CONCLUSION: The significant role of adiponectin in the pathophysiology of MS in premenopausal and postmenopausal women is confirmed in this study. Leptin is correlated with several MS components but this adipocytokine appears to play a role only in postmenopausal women.     

Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression

Adipokines are predominantly secretory protein hormones from adipose tissue but may also originate in placenta and other organs. Cross-sectionally, we monitored maternal plasma concentration of adiponectin, resistin, and leptin and their mRNA expression in abdominal subcutaneous adipose tissue and placenta from preeclamptic (PE; n = 15) and healthy pregnant (HP; n = 23) women undergoing caesarean section. The study groups were similar in age and BMI, whereas HOMA-IR tended to be higher in the PE group. In fasting plasma samples, the PE group had higher concentrations of adiponectin (18.3 +/- 2.2 vs. 12.2 +/- 1.1 microg/ml, P = 0.011), resistin (5.68 +/- 0.41 vs. 4.65 +/- 0.32 ng/ml, P = 0.028), and leptin (34.4 +/- 3.2 vs. 22.7 +/- 2.1 ng/ml, P = 0.003) compared with the HP group. Adiponectin and leptin concentrations were still different between PE and HP after controlling for BMI and HOMA-IR, whereas resistin concentrations differed only after controlling for BMI but not HOMA-IR. We found similar mean mRNA levels of adiponectin, resistin, and leptin in abdominal subcutaneous adipose tissue in PE and HP women. When data were pooled from PE and HP women, resistin mRNA levels in adipose tissue also correlated with HOMA-IR (r = 0.470, P = 0.012) after controlling for BMI and pregnancy duration. Resistin mRNA levels in placenta were not significantly different between PE and HP, whereas leptin mRNA levels were higher in PE placenta compared with HP. Thus increased plasma concentrations of adiponectin and resistin in preeclampsia may not relate to altered expression levels in adipose tissue and placenta, whereas both plasma and placenta mRNA levels of leptin are increased in preeclampsia.     

Age, insulin, SHBG and sex steroids exert secondary influence on plasma leptin level in women

AIM: As the link between body fat and leptin is well known, the aim of the study was to seek for secondary regulators of plasma leptin level. PATIENTS: 86 women (mean: age 47.0+/-14.3 years; estradiol 50.0+/-60.6 ng/l; FSH 52.4+/-42.9 IU/l; BMI 26.9+/-5.9) divided into three groups according to their BMI. Group A: 39 normal weight women (mean: age 44.4+/-16.0 years; estradiol 69.6+/-79.8 ng/l; FSH 50.4+/-47.7 IU/l; BMI 22.9+/-1.3). Group B: 27 overweighted women (mean: age 55.0+/-6.4 years; estradiol 25.1+/-17.2 ng/l; FSH 75.6+/-26.3 IU/l; BMI 27.7+/-1.6). Group C: 21 obese women with mean: age 48.7+/-12.2 years; estradiol 36.9+/-44.0 ng/l; FSH 42.3+/-36.6 IU/l and BMI 34.6+/-4.9. METHODS: Standard clinical evaluation and hormone evaluation (LH, FSH, prolactin, estradiol, leptin, insulin-like growth factor-I (IGF-I), human growth hormone (hGH), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, dihydroepiandrosterone sulphate (DHEAS), sex hormone binding globin (SHBG) and testosterone were done in basic condition which levels of were measured by RIA kits. Statistical analysis. Shapiro-Wilk test, Mann-Whitney-Wilcoxon u test, Spearman rank correlation coefficient and stepwise multiple regression: p values of 0.05 or less were considered as significant. RESULTS: Taking all women into account (n=86) the plasma leptin level correlated directly with age (r=0.32; p<0.02), body mass (r=0.60; p<0.001), BMI (r=0.71; p<0.001) as well as inversely with estradiol (r=-0.21; p<0.05), IGF-I (r=-0.24; p<0.05), SHBG (r=-0.34; p<0.01) and DHEAS (r=-0.30; p<0.01). However only in the group B leptin/age relation remained (r=0.40; p<0.05) after the division according to BMI. In the group B the leptin /DHEAS (r=-0.40; p<0.05) and leptin/PRL (r=0.51; p<0.05) links were also present. In the group C the leptin/SHGB relation (r=-0.56; p<0.02) only remained and an association between insulin and leptin was found (r=0.48; p<0.05). The body mass and BMI relation to age were again present only in all 86 women (r=0.30; p<0.002: r=0.36; p<0.001 resp.). Having split the women into groups, these links either disappeared or became inverse (rC=-0.39; p<0.05). Taking into consideration age/leptin relation in all women, the division according to the menopausal status revealed the direct relation in premenopausal women (n=29; r=0.43; p<0.02) and a reverse one in postmenopausal women (n=38; r=-0.32; p<0.05). The plasma leptin level was the highest (p<0.001) in group C (23.2+/-10.4 microg/l) and the lowest was found in the group A (8.9+/-4.1 microg/l). That corresponded with the differences in mean body mass index and mean body mass. The stepwise multiple regression revealed that body mass index accounted for 31% (p<0.001) and plasma SHBG level accounted for 17.7% (p<0.02) of plasma leptin variance in all women. In the group A body mass and age together accounted for 61% (p<0.01) and estradiol alone accounted for 44% (p<0.02) of plasma leptin variance. In the group B insulin alone accounted for 39% (p<0.05) and together with testosterone accounted for 46% (p<0.05) of plasma leptin variance. Finally in obese women none of the evaluated parameters significantly accounted for leptin variance. CONCLUSION: The results presented in this paper confirmed the strong influence of body fat mass on serum leptin concentration. However insulin, SHBG, sex steroids as well as age may also exert secondary influence on plasma leptin level in certain groups of women.     

Leptin levels in menopause: effect of estrogen replacement therapy

To evaluate the effect of menopause and estrogen replacement therapy on leptin levels, 17 white postmenopausal women were recruited for the study. After an overnight fasting, blood samples were collected for LH, FSH, estradiol, testosterone, androstenedione, DHEA sulfate, insulin and leptin assays. Body mass index (BMI) and the waist-to-hip ratio were also evaluated. Patients were reanalyzed after a 12-week administration of transdermal estrogen patches delivering 50 microg 17beta-estradiol. The results were compared to those obtained from a group of 11 female volunteers in reproductive age, in whom basal blood was sampled during the early follicular phase of their cycle. Patients were divided into lean and obese according to their BMI. Obese postmenopausal women showed lower leptin levels when compared to premenopausal counterparts (25.1 +/- 5.9 vs. 37 +/- 11.3; p < 0.05), whereas no significant differences were found between the lean groups (14.5 +/- 3.8 vs. 14.4 +/- 4.9). Estrogen administration did not significantly change serum leptin concentrations in hypoestrogenized women (obese: 25.1 +/- 5.9 vs. 28. 6 +/- 9.2; lean: 14.4 +/- 4.9 vs. 17.6 +/- 7.2). A positive linear correlation was found between leptin plasma levels and BMI only in obese patients (r = 0.58; p < 0.01) both before and after estrogen treatment. Menopause is characterized by a decreased expression of the obese gene, even if estrogens do not seem to represent a main causal factor.     

Serum leptin and adiponectin concentrations in patients infected with human immunodeficiency virus type 1 (HIV-1) on antiretroviral therapy

The lipodystrophy syndrome with dyslipidaemia and insulin resistance is side-effect of combined antiretroviral therapy (CART). Aim of the study: to describe the influence of CART on leptin and adiponectin concentration in connection with lipids levels in HIV-infected patients on antiretroviral therapy. BMI, serum leptin, adiponectin, triglycerides, total cholesterol, HDL- and LDL-cholesterol concentrations were measured in 56 HIV(+) patients before and on CART; average of treatment duration 38.4 +/-13.2 months. Significant increase of BMI (p=0.0268) of (22.6 +/- 3.3 before and 23.5 +/- 3.4 kg/m2 on therapy, respectively) and all analyzed lipids were found. Mean adiponectin concentration in treated patients was significantly (7.256 +/- 3.551 microg/ml) lower than mean value before treatment (8.395 +/- 3.568 microg/ml; p=0.0011). Mean values of leptin concentrations did not differ significantly (before therapy 3.721 +/- 0.347 log10; on therapy 3.1737 +/- 0.353 log10). Significant positive correlation between BMI and leptin concentrations was found before, as well as during CART (r=0.5333; p<0.0001), but negative correlation between adiponectin and leptin concentrations (r=-0.2677; p=0.042). Leptin and adiponectin concentrations did not revealed significant correlation with lipids levels before therapy. The decrease of adiponectin concentration on CART correlated negatively with total (r=-0.2912; p=0.0310) and LDL-cholesterol (r=-0.310; p=0.0225). CART lasting longer than 2 years resulted in the decrease of adiponectin concentration, with lack of influence on leptin concentration in analyzed group. The increase of total cholesterol and LDL-cholesterol in correlation with the decrease of adiponectin concentration confirms that CART induces metabolic disturbances related to higher risk of atherosclerosis and its sequel.     

Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women

Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc might play an important role in appetite regulation and its administration stimulates leptin production. However, there are few reports in the literature on its role on leptin levels in the obese population. The present work assesses the effect of zinc supplementation on serum leptin levels in insulin resistance (IR). A prospective double-blind, randomized, clinical, placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese women (age: 25-45 yr, body mass index [BMI] = 36.2 +/- 2.3 kg/m2) were randomized for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were similar for age, BMI, caloric intake, insulin concentration, insulin resistance, and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and leptin were measured by radioimmunoassay and IR was estimated by the homeostasis model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and 24- h urine were performed by using atomic absorption spectrophotometry. After 4 wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did not change in either group, although zinc concentration in the urine increased from 385.9 +/- 259.3 to 470.2 +/- 241.2 +/- microg/24 h in the group with zinc supplementation (p < 0.05). Insulin did not change in the placebo group, whereas there was a significant decrease of this hormone in the supplemented group. HOMA also decreased from 5.8 +/- 2.6 to 4.3 +/- 1.7 (p < 0.05) in the zinc-supplemented group but did not change in the placebo group. Leptin did not change in the placebo group. In the zinc group, leptin was 23.6 +/- 12.3 microg/L and did not change. More human data from a unique population of obese individuals with documented insulin resistance would be useful in guiding future studies on zinc supplementation (with higher doses or longer intervals) or different measures.     

Influence of insulin-like growth factor-1 and leptin on bone mineral content in healthy premenopausal women

The aim of the present investigation was to study the influence of plasma insulin-like growth factor-1 (IGF-1) and leptin levels on bone mineral mass (BMC) and bone mineral density (BMD) in premenopausal women and the relationship between IGF-1 and leptin levels. Two hundred and four healthy women participated in this study. All participants had a body mass index (BMI) <30 kg/m(2) and were matched for their level of mean daily energy expenditure. BMC and BMD were correlated with measured body composition and blood biochemical parameters. No association was observed between BMC and BMD values with measured physical performance characteristics. Leptin had a significant association with BMC (beta = 0.840; P = 0.0001), total BMD (beta = 0.833; P = 0.0001), femoral neck BMD (beta = 0.829; P = 0.0001), and lumbar spine BMD (beta = 0.833; P = 0.0001). However, these associations were no longer independent when adjusted for body fat mass (FM) and trunk fat:leg fat ratio (P > 0.385). IGF-1 was significantly related to BMC (beta = 0.920; P = 0.0001), total BMD (beta = 0.918; P = 0.0001), femoral neck BMD (beta = 0.921; P = 0.0001), and lumbar spine BMD (beta = 0.917; P = 0.0001), but did not remain significant when adjusted for fat free mass (FFM; P > 0.062). In addition, a significant association between IGF-1 and leptin was found (beta = 0.801; P = 0.0001), and it remained significant after controlling for age, FM, FFM, insulin, and fasting insulin resistance index (FIRI), but not when adjusted for BMC and body mass values. In conclusion, it appears that fasting IGF-1 and leptin concentrations have no direct effect on BMC and BMD values. In addition, if there is an important relationship between IGF-1 and leptin, it is mediated or confounded by BMC in premenopausal women.     

The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women

The aim of our study was to determine whether adipocyte-derived hormones leptin, adiponectin and resistin contribute to the improvement of insulin sensitivity after very-low calorie diet (VLCD). Therefore, serum levels of these hormones were measured in fourteen obese females before and after three weeks VLCD and in seventeen age- and sex-matched healthy controls. Body mass index, HOMA index, serum insulin and leptin levels in obese women before VLCD were significantly higher than in control group (BMI 48.01+/-2.02 vs. 21.38+/-0.42 kg/m(2), HOMA 10.72+/-2.03 vs. 4.69+/-0.42, insulin 38.63+/-5.10 vs. 18.76+/-1.90 microIU/ml, leptin 77.87+/-8.98 vs. 8.82+/-1.52 ng/ml). In contrast, serum adiponectin and soluble leptin receptors levels were significantly lower in obese women before VLCD than in the control group. No differences were found in serum glucose and resistin levels between the obese group before VLCD and the control group. VLCD significantly decreased BMI, HOMA index, serum glucose, insulin and leptin levels and increased soluble leptin receptor levels. The changes in serum adiponectin and resistin levels in obese women after VLCD did not reach statistical significance. We conclude that leptin and soluble leptin receptor levels were affected by VLCD while adiponectin and resistin concentrations were not. Therefore, other mechanisms rather than changes in the endocrine function of the adipose tissue are probably involved in the VLCD-induced improvement of insulin sensitivity.     

Effect of prolonged training period on plasma adiponectin in elite male rowers.

Adiponectin is secreted by adipocytes and has been implicated in the regulation of energy homeostasis. Vigorous training program represents a physical stress condition in which heavy changes in energy expenditure might increase adiponectin concentration in athletes. Therefore, the aim of the present study was to investigate if there are changes in fasting adiponectin concentration during preparatory period in elite male rowers. Twelve rowers (mean and SD; age: 20.8+/-3.0 years; height: 192.9+/-4.7 cm; body mass: 91.9+/-5.3 kg; body fat percentage: 11.9+/-1.4%) were tested seven times over a 24-week training season. In addition to adiponectin, leptin, insulin, growth hormone, and glucose values were evaluated. Maximal oxygen consumption (VO (2 max)) and aerobic power (Pa (max)) were determined before and after the training period. Training was mainly organized as low-intensity prolonged training. Significant increases in VO (2 max) (by 3.2+/-1.8%; from 6.2+/-0.5 to 6.4+/-0.4 l/min), VO (2 max/kg) (by 2.2+/-2.0%; from 67.9+/-3.0 to 69.4+/-3.0 ml/min/kg) and Pa (max) (by 4.6+/-6.3%; from 444.6+/-39.1 to 465.8+/-25.0 W) were observed after the 24-week period. All measured body compositional values were similar to pretraining values after the training period. Fasting adiponectin did not change during the preparatory period. Likewise, leptin, insulin, growth hormone, and glucose values were not significantly changed after the training period. Adiponectin concentration was significantly correlated (all p<0.05) with body mass (r=-0.40), body fat mass (r=-0.33), body fat free mass (r=0.38), and leptin (r=-0.31) values. In conclusion, fasting adiponectin does not change throughout the prolonged training period in elite male rowers despite substantial changes in training volume. Further studies are needed to clarify possible mechanisms by which adiponectin might influence energy homeostasis during heavy training in elite athletes.     

Leptin in type 2 diabetic or myotonic dystrophic women.

BACKGROUND: Insulin resistance is an important determinant of circulating leptin concentrations in humans, but its independent contribution on plasma leptin levels are controversial. In the present study, we characterized plasma leptin levels and their regulation in women with 2 different insulin resistance states: type 2 diabetes and myotonic dystrophy disease, and in controls. MATERIAL AND METHODS: We studied 3 groups of women: 21 type 2 diabetic patients, 20 myotonic dystrophic patients and a control group of 20 normoglycemic subjects, matched in age and body mass index. Body composition, fasting glucose and insulin, IGF-I, IGF-binding protein-3 and leptin were studied. Body composition was measured using a bioelectrical impedance analyser. Insulin sensitivity (in percentage) was modeled according to a computer-based homeostasis model assessment model. Data are expressed in mean +/- SEM. RESULTS: In both groups of patients, glucose concentrations were higher in type 2 diabetic patients than in myotonic dystrophic patients, and insulin concentrations and insulin sensitivity were similar in the 2 groups of patients (82.4 +/- 18.6% in type 2 diabetic patients vs. 69.7 +/- 9.7% in myotonic dystrophic patients, p = 0.2) and lower than in controls. Serum leptin and leptin/fat mass ratio were higher in myotonic dystrophic patients than in type 2 diabetic patients (30 +/- 4.9 ng/ml vs. 17.7 +/- 2.6 ng/ml, p = 0.03 and 2.32 +/- 0.69 ng/ml/kg vs. 1.07 +/- 0.2 ng/ml/kg, p = 0.02, respectively) or those found in controls. In type 2 diabetic patients, leptin concentrations were correlated with body mass index and body fat, and in myotonic dystrophic patients leptin concentrations were correlated with age, body mass index, fasting insulin and lower insulin sensitivity, whereas leptin concentrations were not correlated with body fat. CONCLUSIONS: These findings suggest that leptin concentrations and regulation in myotonic dystrophic patients are different from type 2 diabetes.     

Adiponectin mRNA levels in parametrial adipose tissue and serum adiponectin levels are reduced in mice during late pregnancy.

Adiponectin, a fat-derived factor, is downregulated in insulin resistance and obesity; insulin resistance has been demonstrated during late pregnancy in both humans and in rodents. The present study examines the physiological change of adiponectin gene expression as well as the circulating levels of adiponectin during pregnancy. We examined the relative quantity of adiponectin mRNA produced in the adipose tissues of pregnant compared to virgin mice. We also measured serum adiponectin levels and parametrial adipocyte size in mice throughout pregnancy. Adiponectin mRNA was significantly reduced by 74 +/- 8 % and 63 +/- 4 % at days 15 and 18 of pregnancy, respectively, compared to virgin mice. Serum adiponectin concentration decreased on days 15 (30.7 +/- 8.5 microg/ml) and 18 (27.9 +/- 8.7 microg/ml) of pregnancy, and the values were significantly lower than that of virgin mice (56.8 +/- 6.6 microg/ml). Parametrial adipocytes from mice on days 15 and 18 of pregnancy were significantly larger than in virgin mice or during early pregnancy. Fat-cell size was closely correlated to degradation of adiponectin gene expression and serum adiponectin levels. These results suggest that changes of adiponectin expression affect metabolic status in pregnant mice.     

Influence of bone mineral density in circulating adipokines among postmenopausal Arab women

Osteoporosis and osteopenia has a significant link with substantial fracture risk. Epidemiological data revealed a protective role of adipose tissue on bone biology in postmenopausal osteoporosis. The current study assessed the associations between select adipokines and bone mineral density (BMD) in postmenopausal women. A total of 175 Saudi postmenopausal women were selected and categorized based on their BMD (normal & low-BMD). Circulating levels of select adipokines (adiponectin, resistin, leptin, and adipsin), insulin, 25(OH)D and RANKl were determined using commercially available assay kits. BMD was measured by dual-energy X-ray absorptiometry (DXA). Overall and among low-BMD subjects, adiponectin consistently showed a significant inverse association with BMD (overall −0.34, p < 0.01; low BMD group −0.34, p < 0.01). In multiple regression, adiponectin (−0.29 ± 0.06, p < 0.00) and resistin (−0.08 ± 0.04, p < 0.05) were inversely significant with BMD overall, but after stratification the significance was lost for resistin (−0.05 ± 0.04, p < 0.224) whereas adiponectin remained (−0.22 ± 0.07, p < 0.02) in low-BMD subjects. Adipsin, leptin and lipocalin-2 showed no significant associations. Findings of the present study revealed that only adiponectin showed a significantly strong inverse association with low BMD, suggesting that insulin sensitivity may influence bone health in Arab postmenopausal women.     

The relationship between insulin sensitivity and serum adiponectin levels in three population groups.

Reduced plasma adiponectin levels are associated with insulin resistance. Black South Africans, like African Americans, are more insulin-resistant than BMI-matched white subjects, as are Asian Indians. We investigated whether this interethnic variation in insulin resistance is due to differences in plasma adiponectin levels. Blood and anthropometric measurements were taken from black, white and Asian-Indian subjects. Serum adiponectin, lipids, glucose and insulin were measured; insulin sensitivity was calculated using HOMA. Black (HOMA = 2.62 +/- 0.99) and Asian-Indian subjects (HOMA = 3.41 +/- 2.85) were more insulin-resistant than BMI-matched white (HOMA = 1.76 +/- 0.63) subjects (p = 0.0001). Furthermore, the white subjects had higher adiponectin levels (8.11 +/- 4.39 microg/ml) compared to black (5.71 +/- 2.50 microg/ml) and Asian Indian (5.86 +/- 2.50 microg/ml) subjects (p = 0.003). When all ethnic groups were combined, multiple regression analysis demonstrated that serum adiponectin levels corrected for BMI and ethnicity did not correlate with HOMA, but did explain 10.0 % of the variance in HDL-cholesterol levels. Within each ethnic group, adiponectin only correlated inversely with HOMA in white subjects. Adiponectin may play a role in determining serum HDL-cholesterol levels, but ethnic variation in insulin sensitivity is not dependent on serum levels of this adipokine. The relationship between adiponectin and insulin resistance varies across ethnic groups.     

Insulin resistance,intramyocellular lipid content,and plasma adiponectin in patients with type 1 diabetes

Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2H2]glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 +/- 0.6 and 3.2 +/- 0.8 ml x kg(-1) min(-1)) similar to OFF (5.3 +/- 0.4 ml x kg(-1) x min(-1)) compared with NOR (8.5 +/- 0.5 ml x kg(-1) min(-1), P < 0.001). Soleus IMCL content was increased in T1DM (112 +/- 15 AU), T2DM (108 +/- 10 AU) and OFF (82 +/- 13 AU) compared with NOR (52 +/- 7 AU, P < 0.05) and the result was inversely proportional to the MCR (R2 = 0.27, P < 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R2 = 0.57, P < 0.001). Fasting plasma adiponectin was reduced in T2DM (7 +/- 1 microg/ml, P = 0.01) and OFF (11 +/- 1 microg/ml, P = 0.03) but not in T1DM (25 +/- 6 microg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 +/- 2 microg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.     

Relationship of Leptin Concentration to Gender,Menopause, Age,Diabetes, and Fat Mass in African Americans

This investigation was designed to determine the relationship of leptin concentration to gender, sex hormones, menopause, age, diabetes, and fat mass in African Americans. Participants included 101 African Americans, 38 men (mean age, 34. 2 ± 7. 4 years), 29 age-matched premenopausal women (mean age, 32. 6 ± 3. 7 years), and 36 postmenopausal women (mean age, 57. 8 ± 5. 9 years). The women were not taking exogenous sex hormones, and 12 subjects were diabetic. Percent body fat was calculated with the Siri formula, fat mass (FM) was calculated as weight x percent body fat, and Fat-free mass (FFM) was calculated as weight minus FM. Fasting plasma was assayed for leptin, estradiol, free testosterone, glucose, and insulin concentrations. The nondiabetics had an oral glucose tolerance test (OGTT). The diabetics compared with the non-diabetics had a higher central fat index (^P=0. 04) but otherwise were similar to nondiabetics in all parameters measured. Body mass index, percent body fat, and FM were greater in women than men (p<0. 001). Leptin concentrations in men, premenopausal, and postmenopausal women were: 7. 51 ± 8. 5, 33. 9 ± 17. 3, 31. 4 ± 22. 3 ng/mL. Leptin/FM x 100 in the three groups were: 28. 9 ± 16. 1, 98. 65 ± 44. 9, 77. 1 ± 44. 5 ng/mL/kg. The gender difference in leptin concentration and leptin/FM was significant (p<0. 001), but the difference between premenopausal and postmenopausal women was not. In each group, weight, percent body fat, and FM were highly correlated with leptin concentration. Multiple regression analyses with leptin concentration as the dependent variable and age, diabetic status, percent body fat, weight, FM, FFM, estradiol, and free testosterone concentrations as independent variables demonstrated that the determinants of leptin concentration in men was weight only (R=0. 83,p<0. 001), in premenopausal women it was FM only (R=0. 57,P<0. 001), and in postmenopausal women it was weight only (R=0. 67, p<0. 001). With diabetics excluded, the multiple regression analysis was repeated with fasting insulin concentration and the area under the insulin curve during the OGTT included as independent variables. The results for this multiple regression analyses were the same as the first. Therefore, leptin concentration in African Americans is determined by gender and fat mass. Menopause, age, and diabetes do not affect leptin concentration.     

Short-term fasting abolishes the sex-related difference in GH and leptin secretion in humans

We studied growth hormone (GH) and leptin secretion in eight male (age 29.3 +/- 1.2 yr, body mass index 22.2 +/- 0.5 kg/m(2)) and seven female normal subjects (28.0 +/- 0.8 yr, 20.1 +/- 0.7 kg/m(2)) before and after 36 h of fasting. In the fed state, 8-h mean GH and leptin concentrations were higher in females (P < 0.05 and P < 0. 0001, respectively). Fasting increased GH and decreased leptin in both sexes. There was significant interaction between gender and fasting (P < 0.05 for GH and P < 0.005 for leptin). Females showed a slighter increase in GH but a more marked decrease in leptin, so that there was no significant gender-related difference in GH and leptin after fasting. Fasting did not modify insulin-like growth factor (IGF) I, IGF binding protein (IGFBP)-3, acid-labile subunit, or GH binding protein; increased IGFBP-1 and free fatty acids (P < 0.0001) but decreased glucose (P < 0.001) and insulin levels (P < 0.05). In males, insulin levels were higher (P < 0.05) in the fed state and underwent deeper reduction after fasting (interaction P < 0.03). In conclusion, GH and leptin secretions are higher in women than in men in the fed but not in the fasting condition, which abolishes these gender-related differences in humans.     

Secretion of neuropeptide Y in human adipose tissue and its role in maintenance of adipose tissue mass

NPY is an important central orexigenic hormone, but little is known about its peripheral actions in human adipose tissue (AT) or its potential paracrine effects. Our objective was to examine NPY's role in AT, specifically addressing NPY protein expression, the effect of NPY on adipokine secretion, and the influence of insulin and rosiglitazone (RSG) on adipocyte-derived NPY in vitro. Ex vivo human AT was obtained from women undergoing elective surgery [age: 42.7 +/- 1.5 yr (mean +/- SE), BMI: 26.2 +/- 0.7 kg/m(2); n = 38]. Western blot analysis was used to determine NPY protein expression in AT depots. Abdominal subcutaneous (AbSc) adipocytes were isolated and treated with recombinant (rh) NPY, insulin, and RSG. NPY and adipokine levels were measured by ELISA. Our results were that NPY was localized in human AT and adipocytes and confirmed by immunohistochemistry. Depot-specific NPY expression was noted as highest in AbSc AT (1.87 +/- 0.23 ODU) compared with omental (Om; 1.03 +/- 0.15 ODU, P = 0.029) or thigh AT (Th; 1.0 +/- 0.29 ODU, P = 0.035). Insulin increased NPY secretion (control: 0.22 +/- 0.024 ng/ml; 1 nM insulin: 0.26 +/- 0.05 ng/ml; 100 nM insulin: 0.29 +/- 0.04 ng/ml; 1,000 nM insulin: 0.3 +/- 0.04 ng/ml; P < 0.05, n = 13), but cotreatment of RSG (10 nM) with insulin (100 nM) had no effect on NPY secretion. Furthermore, adipocyte treatment with rh-NPY downregulated leptin secretion (control: 6.99 +/- 0.89 ng/ml; 1 nmol/l rh-NPY: 4.4 +/- 0.64 ng/ml; 10 nmol/l rh-NPY: 4.3 +/- 0.61 ng/ml, 100 nmol/l rh-NPY: 4.2 +/- 0.67 ng/ml; P < 0.05, n = 10) but had no effect on adiponectin or TNF-alpha secretion. We conclude that NPY is expressed and secreted by human adipocytes. NPY secretion is stimulated by insulin, but this increment was limited by cotreatment with RSG. NPY's antilipolytic action may promote an increase in adipocyte size in hyperinsulinemic conditions. Adipose-derived NPY mediates reduction of leptin secretion and may have implications for central feedback of adiposity signals.