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.     

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.     

Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size

Introduction

Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood.

Methods

For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG) patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation.

Results

The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p < 0.01) indicating significant infiltration of macrophages. Statin treated patients showed significantly lower epicardial expression of IL-6 mRNA, in comparison with the control abdominal depots (p < 0.001). The serum profile of CABG patients showed significantly higher levels of both CRP (control: 1.28 ± 1.57 μg/mL vs CABG: 9.11 ± 15.7 μg/mL; p < 0.001) and resistin (control: 10.53 ± 0.81 ng/mL vs CABG: 16.8 ± 1.69 ng/mL; p < 0.01) and significantly lower levels of adiponectin (control: 29.1 ± 14.8 μg/mL vs CABG: 11.9 ± 6.0 μg/mL; p < 0.05) when compared to BMI matched controls.

Conclusion

Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

Elevated serum triglycerides is the strongest single indicator for the presence of metabolic syndrome in patients with type 2 diabetes

Objectives

South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels.

Methods

In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA).

Results

Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01.

Conclusion

Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance.     

Unchanged Serum Adipokine Concentrations in the Setting of Short-Term Thyroidectomy-Induced Hypothyroidism

ObjectiveTo investigate short-term effects of thyroidectomy-induced hypothyroidism on leptin, adiponectin, and resistin concentrations in association with anthropometric data.MethodsThirty premenopausal women with euthyroid nodulargoiter-mean age, 44.0 ± 11.6 years; mean body mass index (BMI), 28.6 ± 5.9 kg/m²; 13 obese, 7 overweight, and 10 normal weight subjects—scheduled for total thyroidectomy were included in the study. Serum leptin, adiponectin, resistin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, glucose, insulin, and C-reactive protein concentrations, lipid profile, and anthropometric variables were determined in the euthyroid state (preoperatively) and the hypothyroid state (postoper atively, with a thyroid-stimulating hormone concentration > 30 mIU/L).ResultsBody weight, BMI, waist and hip circumferences, body fat mass, and serum lipid concentrations increased significantly after thyroidectomy. No significant difference was found between preoperative and postoperative serum leptin, adiponectin, and resistincon centrations. Fat tissue mass-corrected leptin, adiponectin, and resistin concentrations did not differ significantly between euthyroid and hypothyroid periods. Thyroid hor mone concentrations showed no significant correlations with adipokine levels.ConclusionSerum adipokine concentrations seem not to change significantly during short-term thyroidec tomy-induced hypothyroidism despite significant increases in body weight, BMI, fat mass, and lipid concentrations.(Endocr Pract. 2012;18:887-893)     

A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women

Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1‐year follow‐up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6‐month exercise‐based weight loss program and returned for follow‐up at 18 months. Dual‐energy X‐ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m². They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow‐up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (?1.7 ± 3.5%; P = 0.002) and hip (?0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C‐terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (?0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: ?3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone‐deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.     

Plasma Leptin Response to an Epinephrine Infusion in Lean and Obese Women

Objective: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. Research Methods and Procedures: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 μg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index ± SD: 22.6 ± 1.1 kg/m²) and 15 obese (30.0 ± 1.3 kg/m²) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (−15 and 0 minutes) and at every 30 minutes over the 90-minute period. Results: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = −0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from −12 to −570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = −0.14, p = 0.55). Discussion: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.     

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm²).ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)     

Leptin to adiponectin ratio as a useful predictor for cardiac syndrome X

Objective: The role of adipokines in the development of cardiac syndrome X (CSX) remains unknown.

Methods: Fifty-nine CSX subjects were retrospectively enrolled from our catheterization databank. Another 54 subjects with valvular heart disease or arrhythmia served as controls. Adipokines were measured by ELISA tests.

Results: The CSX had lower circulating adiponectin but higher leptin and higher leptin/adiponectin ratio (×1000) (3.78?±?4.96 vs. 2.14?±?5.67, p < 0.001) than those of the controls. In a multivariate analysis, a higher leptin/adiponectin ratio was a predictor of CSX, while insulin-resistance index was not.

Conclusions: Adipokines may be implicated in the pathogenesis of CSX.     

Correlation Between Bone Markers and Bone Mineral Density in Postmenopausal Women with Osteoporosis

ObjectiveTo study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.MethodsEighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Patients with low serum vitamin D levels, secondary osteoporosis, or clinically significant systemic disease were excluded from the study. The patients were classified on the basis of BMD of the lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through -3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score ≤-4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < .05 being considered significant.ResultsSerum osteocalcin was significantly different among the 3 study groups (4.1 ± 2.7, 4.5 ± 3.1, and 6.7 ± 5.6 ng/mL, respectively; P = .0349) and had a significant negative correlation with BMD (r² = -0.0779; P = .0168). Other bone markers such as bone-specific alkaline phosphatase and urinary free deoxypyridinoline did not correlate with the underlying BMD.ConclusionIn our study, osteocalcin was significantly correlated with BMD in postmenopausal women with osteoporosis. Other bone markers did not correlate with BMD. Further large-scale population data and analyses are needed to confirm these findings. (Endocr Pract. 2008;14:1102-1107)     

Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals

Objectives

We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA.

Methods

Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA), without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27). Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry.

Results

The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2); p = 0.020), also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5); p = 0.016). This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529) and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520) and ESR (leptin r = 0.512, chemerin r = 0.708), p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis.

Conclusions

In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals.     

Long non-coding RNA-DANCR in human circulating monocytes: a potential biomarker associated with postmenopausal osteoporosis

Osteoporosis is a common disease characterized by low bone mineral density (BMD) and low trauma fractures, mainly resulting from exceeding bone resorption by osteoclasts over bone formation by osteoblasts. Circulating monocytes are directly involved in osteoclastogenesis, and lncRNAs are believed to be involved in the osteoblast differentiation. However, no study has been conducted to identify the roles of lncRNA in circulating monocytes associated with human osteoporosis. In this study, we found significant upregulation of DANCR in the blood mononuclear cells (MNCs) from low-BMD patients with the qRT-PCR analyses. We further found that DANCR promoted the expression of IL6 and TNF-α at both mRNA level and protein level in MNCs. After deletion of DANCR with siRNAs, the levels of IL6 and TNF-α are decreased in the MNCs from low-BMD postmenopausal women. Moreover, DANCR level was correlated with IL6 and TNF-α in postmenopausal women with low BMD. Furthermore, we found that DANCR-induced IL6 and TNF-α in MNCs had bone-resorbing activity. These results indicate that DANCR is involved in the pathology of osteoporosis and may be as a biomarker for postmenopausal osteoporosis.     

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco’s modified Eagle’s medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10⁻⁸–10⁻⁷ M), progesterone (10⁻⁶–10⁻⁵ M), the Rho-kinase inhibitor, Y-27632 (10⁻⁵ M) and their combination for 8 days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation.     

Gender Differences in the Response of Plasma Leptin Concentrations to Weight Loss in Obese Older Individuals

Plasma leptin concentration is directly related to the degree of obesity and is higher in women than in men of the same body mass index (BMI). We hypothesized that fasting plasma leptin concentrations and the response of leptin to weight loss would differ in older men and women of a similar fat mass. Plasma leptin concentrations (radioimmunoassay) and fat mass (DXA) were measured in 47 older, obese (BMI=30 ± 4 kg/m²) women and 23 older, obese (BMI=31 ± 3 kg/m²) men after a 2 to 4 week period of weight and dietary stabilization, and then in 22 of the women and 18 of the men after a 6-month weight loss intervention (250–350 kcal/d deficit). Leptin correlated with fat mass in men and women (r=0.75 and r=0.77, respectively; p values<0.0001), but women had 3-fold higher leptin levels for a given fat mass than men (p=0.01). In response to the 6-month hypocaloric diet, men and women lost a similar percentage of fat mass (?13% and ?16%, respectively), but the relative decline in circulating leptin was greater in women than men (-45% and ?21%, respectively; p<0.0001). In addition, when leptin was normalized for fat mass using the ratio method, the decrease in leptin per kilogram of fat mass was greater in women than men (-0.37 ± 0.34 vs. ?0.04 ± 0.06 ng/mL/kg; p<0.01). After weight loss, the change in leptin concentrations correlated positively with the change in fat mass in men (r=0.60; p<0.01), but not in women (r=0.31; p=0.17). Furthermore, the loss in fat mass correlated negatively with baseline leptin levels in women (r=-0.47; p<0.05), but not in men (r=0.03, p=NS). These results indicate that the decline in leptin concentration with weight loss correlates with the loss in fat mass in men; but, in women, other factors affect the decrease in leptin concentration. This suggests that the role of leptin in the regulation of obesity is gender-specific and may account for gender differences in response to hypocaloric treatment and maintenance of lost weight.     

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.     

Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein activity are associated with leptin in type 2 diabetes mellitus

Adipose tissue contributes to plasma levels of lipid transfer proteins and is also the major source of plasma adipokines. We hypothesized that plasma cholesteryl ester transfer protein (CETP) mass, phospholipid transfer protein (PLTP) activity and cholesteryl ester transfer (CET, a measure of CETP action) are determined by adipokine levels. In this study, relationships of plasma CETP mass, PLTP activity and CET with leptin, resistin and adiponectin were analyzed in type 2 diabetic patients and control subjects. Plasma PLTP activity (P<0.001), CET (P<0.001), leptin (P=0.003), resistin (P<0.001), high sensitive C-reactive protein (P=0.005), and insulin resistance (HOMA(ir)) (P<0.001) were higher, whereas HDL cholesterol (P<0.001) and plasma adiponectin (P<0.001) were lower in 83 type 2 diabetic patients (32 females) than in 83 sex-matched control subjects. Multiple linear regression analysis demonstrated that in diabetic patients plasma leptin levels were related to plasma CETP mass (P=0.018) and PLTP activity (P<0.001), but not to the other adipokines measured. Plasma CET was inversely correlated with adiponectin in univariate analysis, but this association disappeared in multivariate models that included plasma lipids and CETP. In conclusion, both plasma CETP mass and PLTP activity are associated with plasma leptin in type 2 diabetes. The elevated CET in these patients is not independently related to any of the measured plasma adipokines.     

Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables

The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but <7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) <30 kg/m(2). Adiponectin values were higher (P < 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/- 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P < 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P < 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle-aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status.     

Adipokines in Psoriatic Arthritis Patients: The Correlations with Osteoclast Precursors and Bone Erosions

Significant bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of psoriatic arthritis (PsA). And there is a high prevalence of the metabolic syndrome (MS) in PsA patients. Adipokines, especially leptin and adiponectin, have recently been reported to be involved in the development and regulation of some autoimmune diseases. In this study, we examined the alternation of circulating osteoclastogenesis related cytokines [tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL)] and adipokines (leptin, adiponectin, resistin, chemerin, omentin) in PsA patients, and analysed the correlations between these factors and osteoclast precursors numbers, radiographic damage scores, and disease activity index. 41 PsA patients, 20 psoriasis patients, and 24 healthy controls were recruited. Blood samples were obtained for detecting the levels of TNF-α, OPG, RANKL and the adipokines. The numbers of osteoclast precursors (OCs) in peripheral blood were assessed. Radiographs of affected joints in PsA patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Compared with healthy controls, patients with PsA had higher TNF-α, RANKL, OCs, leptin and omentin but lower adiponectin and chemerin. Increased serum levels of TNF-α, RANKL, leptin, and omentin were positively correlated with OCs numbers. In contrast, serum adiponectin levels were decreased in PsA patients and negatively correlated with OCs numbers. TNF-α, RANKL and leptin were positively correlated with Psoriatic Arthritis Joint Activity Index (PsAJAI). Only TNF-α was positively correlated with radiographic damage scores. Our data demonstrated that systemic expression of soluble mediators of osteoclastogenesis and adipokines were disordered in PsA. Certain adipokines were elevated in the circulation of patients with PsA and might contribute to pathogenesis of arthritis. Prospective studies will be of interest to determine the pluripotent effects of adipokines on osteoclastogenesis in chronic inflammatory rheumatic diseases. Future studies may lead to novel therapeutic strategies.