Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women

Objective:

Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB‐R) in healthy midlife women.

Design and Methods:

Cross‐sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow‐up visit of the multiethnic Study of Women's Health Across the Nation.

Results:

T was weakly negatively associated with both HMW adiponectin and sOB‐R (r = ?0.12 and r = ?0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB‐R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = ?0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB‐R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB‐R, independent of fat mass.

Conclusions:

These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

     

The Effects of Macronutrient Intake on Total and High‐molecular Weight Adiponectin: Results From the OMNI‐Heart Trial

Higher levels of the adipocyte‐specific hormone adiponectin have been linked to increased high‐density lipoprotein (HDL) and lower insulin resistance. This study was conducted to determine the influence of macronutrient intake on adiponectin levels. One hundred and sixty‐four pre‐ and stage‐1 hypertensive adults participated in the Optimal Macro‐Nutrient Intake Heart (OMNI‐Heart) trial, a crossover feeding study originally testing the effects of macronutrients on blood pressure. Participants underwent three 6‐week feeding periods: one rich in carbohydrates (CARB), one rich in monounsaturated fat (MUFA), and one rich in protein (PROT), while maintaining body weight. Their median plasma high molecular weight (HMW) and total adiponectin levels were 2.3 and 8.2 µg/ml, respectively, resulting in an average of 27% HMW adiponectin. Both HMW and total adiponectin levels decreased after baseline while the percent HMW adiponectin remained unchanged. Between diets, the MUFA diet maintained a higher level of both HMW and total adiponectin levels than either the CARB (HMW: +6.8%, P = 0.02; total: +4.5%, P = 0.001) or PROT (HMW: +8.4%, P = 0.003; total: +5.6%, P < 0.001) diets. Changes in total adiponectin levels were positively correlated to changes in HDL cholesterol irrespective of diets (Spearman r = 0.22–0.40). No correlation was found between changes in lipids, blood pressure, or insulin resistance by the homeostasis model assessment (HOMAIR). Macronutrient intake has effects on HMW and total adiponectin levels independent of weight loss. A diet rich in MUFA was associated with higher levels of total and HMW adiponectin in comparison to a carbohydrate‐ or protein‐rich diet. Effects seen in adiponectin paralleled those found with HDL cholesterol.     

Inflammatory adipokines, high molecular weight adiponectin, and insulin resistance: a population-based survey in prepubertal schoolchildren

Background

The aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.

Methodology

We studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole''s criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk.

Principal Findings

Leptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (p<0.0001) from L to OW to OB boys and girls. When compared with L peers, OW and OB girls exhibited lower (p<0.001) HMW adiponectin levels, while in boys the HMW multimers did not differ significantly across the BMI-stratified groups. OB girls displayed higher (p<0.05) IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 levels (sICAM-1) than L girls, whereas increased macrophage migration inhibitory factor (MIF) concentrations in OB vs OW boys were seen. HMW adiponectin (negatively), leptin or inflammatory markers (positively) correlated with adiposity and IR measures. In multivariate models, leptin represented a strong and independent determinant of HOMA-IR (R² 0.378; p<0.01). Adjustment for age, BMI_z-score, lipids and inflammatory mediators abolished the association between leptin and HOMA-IR in boys, while in girls leptin remained still a significant predictor of IR (R² 0.513; p<0.01). Finally, in both sexes, the joint effect of the L/HMW did not improve the prediction of basal IR as compared with leptin levels alone, which were mainly explained by the BMI_z-score.

Conclusions

In prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance.     

Weight Loss Increases Soluble Leptin Receptor Levels and the Soluble Receptor Bound Fraction of Leptin

Objective: Soluble leptin receptor (sOB‐R) represents the main binding site for leptin in human blood. The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound/free ratio after pronounced weight reduction. Research Methods and Procedures: A total of 18 morbidly obese women participated in this prospective study. Subjects were examined for fat mass, leptin, and sOB‐R concentrations before and 1 year after Swedish adjustable gastric banding. Results: Anthropomorphic measures displayed a significant reduction of body mass index [(42.9 ± 5.6 to 32.9 ± 6.0 kg/m² (mean ± SD)]. Fat mass decreased from 56.3 ± 9.0 to 33.9 ± 12.5 kg. Plasma leptin concentration decreased from 44.6 ± 18.0 to 20.0 ± 13.1 ng/mL (p < 0.001), whereas the sOB‐R levels increased from 11.1 ± 3.6 to 16.6 ± 6.0 U/mL after weight‐reducing surgery. Thus, the sOB‐R bound fraction of leptin increased from 7% to 33%. Discussion: This work demonstrates a relationship between weight loss, leptin, and sOB‐R concentrations in vivo. During weight loss, leptin levels decreased, whereas sOB‐R levels and the receptor bound fraction of leptin increased. Thus, sOB‐R may negatively regulate free leptin.     

Adiponectin Oligomers and Ectopic Fat in Liver and Skeletal Muscle in Humans

We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total‐, high‐molecular weight (HMW)‐, middle‐molecular weight (MMW)‐, and low‐molecular weight (LMW) adiponectin were quantified by an enzyme‐linked immunosorbent assay. Their relationships with liver‐ and intramyocellular fat, measured using ¹H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = ?0.35, P = 0.012), but not with total‐, MMW‐, or LMW adiponectin. In addition, subjects with fatty liver (liver fat ≥5.56%, n = 15) had significantly lower HMW‐ (P = 0.04), but not total‐, MMW‐, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = ?0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.     

Relationships of cardiac autonomic function with metabolic abnormalities in childhood obesity

Objective: The objective was to examine cardiovascular autonomic (cANS) function and its potential relationships with leptin resistance, insulin resistance, oxidative stress, and inflammation in a pediatric sample with varying levels of obesity. Research Methods and Procedures: Participants were normal‐weight (NW; BMI <85th percentile, 6 male, 4 female), overweight (OW; 85th percentile < BMI <95th percentile, 6 male, 4 female), and obese children (OB; BMI >95th percentile, 6 male, 10 female) who had cANS function assessed via heart rate variability (HRV) methods during resting conditions. Standard time‐domain and frequency‐domain measures [high‐frequency normalized units (HFnu; measure of parasympathetic nervous system activity) and low frequency:high‐frequency ratio (LF:HF; overall sympathovagal balance)] of HRV were calculated. Fasting blood samples were drawn for measurement of glucose, insulin, lipids, 8‐isoprostane, leptin, soluble leptin‐receptor (sOB‐R), C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α). Results were reported as mean ± standard error of the mean. Results: OB had significantly elevated LF:HF and decreased HFnu when compared with NW (p < 0.05), but no differences between OW and NW were observed. Measures of HRV were significantly related to leptin, insulin resistance, 8‐isoprostane, and CRP (p < 0.05), but these relationships were not significant after adjustment for fat mass. Discussion: When compared with NW, OB but not OW children are characterized by cANS dysfunction and increased leptin, insulin resistance, oxidative stress, and inflammation (CRP). The relationships between these factors seem to be dependent on quantity of fat mass and/or other factors associated with being obese.     

Changes in Circulating Satiety Hormones in Obese Children: A Randomized Controlled Physical Activity‐Based Intervention Study

The aims of this study are to examine in children: (i) obesity‐related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity‐based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 ± 0.6 for 15 obese and 56.2 ± 1.1 for 6 lean). The obese subjects underwent a 3‐month randomized controlled physical activity‐based lifestyle intervention. Leptin, soluble leptin receptor (sOB‐R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual‐energy X‐ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB‐R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB‐R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity‐based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.     

In Utero Gender Dimorphism of Adiponectin Reflects Insulin Sensitivity and Adiposity of the Fetus

Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular weight (HMW) multimers, the most active forms mediating the insulin‐sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. To further understand the functional properties of adiponectin during fetal life, we have evaluated the associations of adiponectin with insulin sensitivity, body composition, and gender. Umbilical cord adiponectin, adiponectin complexes, and metabolic parameters were measured at term by elective cesarean delivery. The associations between adiponectin, measures of body composition, and insulin sensitivity were evaluated in relation to fetal gender in 121 singleton neonates. Higher total adiponectin concentrations in female compared with male fetuses (34.3 ± 9.5 vs. 24.9 ± 8.6, P < 0.001) were associated with a 3.2‐fold greater abundance in circulating HMW complexes (0.20 ± 0.03 vs. 0.08 ± 0.03, P < 0.001, n = 9). Adiponectin was positively correlated with neonatal fat mass (r = 0.27, P < 0.04) and percent body fat in female fetuses (r = 0.28, P < 0.03) and with lean mass in males (r = 0.28, P < 0.03). There was no significant correlation between cord adiponectin and fasting insulin concentrations or fetal insulin sensitivity as estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). The gender dimorphism for plasma adiponectin concentration and complex distribution first appears in utero. In sharp contrast to the inverse correlation found in adults, the positive relationship between adiponectin and body fat is a specific feature of the fetus.     

Restoration of acute insulin response in T2DM subjects 1 month after biliopancreatic diversion

Objective: Biliopancreatic diversion (BPD) restores normal glucose tolerance in a few weeks in morbid obese subjects with type 2 diabetes, improving insulin sensitivity. However, there is less known about the effects of BPD on insulin secretion. We tested the early effects of BPD on insulin secretion in obese subjects with and without type 2 diabetes. Methods and Procedures: Twenty‐one consecutive morbid obese subjects, 9 with type 2 diabetes (T2DM) and 12 with normal fasting glucose (NFG) were evaluated, just before and 1 month after BPD, by measuring body weight (BW), glucose, adipocitokines, homeostasis model assessment of insulin resistance (HOMA‐IR), acute insulin response (AIR) to e.v. glucose and the insulinogenic index adjusted for insulin resistance ([ΔI5/ΔG5]/HOMA‐IR). Results: Preoperatively, those with T2DM differed from those with NFG in showing higher levels of fasting glucose, reduced AIR (57.9 ± 29.5 vs. 644.9 ± 143.1 pmol/l, P < 0.01) and reduced adjusted insulinogenic index (1.0 ± 0.5 vs. 17.6 ± 3.9 1/mmol², P < 0.001). One month following BPD, in both groups BW was reduced (by ～11%), but all subjects were still severely obese; HOMA‐IR and leptin decreased significanlty, while high‐molecular weight (HMW) adiponectin and adjusted insulinogenic index increased. In the T2DM group, fasting glucose returned to non‐diabetic values. AIR did not change in the NFG group, while in the T2DM group it showed a significant increase (from 58.0 ± 29.5 to 273.8 ± 47.2 pmol/l, P < 0.01). In the T2DM group, the AIR percentage variation from baseline was significantly related to changes in fasting glucose (r = 0.70, P = 0.02), suggesting an important relationship exists between impaired AIR and hyperglycaemia. Discussion: BPD is able to restore AIR in T2DM even just 1 month after surgery. AIR restoration is associated with normalization of fasting glucose concentrations.     

Weight loss and improved gross motor coordination in children as a result of multidisciplinary residential obesity treatment

This study evaluated the short‐term effectiveness of a multidisciplinary residential obesity treatment program by describing changes in body weight, related measures, and gross motor co‐ordination. Secondarily, it was examined to what extent the amount of relative weight loss achieved by overweight and obese (OW/OB) participants explained the projected improvement in gross motor co‐ordination. Thirty‐six OW/OB children (aged 10.5 ± 1.4 years, 12 girls and 24 boys) were recruited at the Zeepreventorium VZW (De Haan, Belgium), where they followed a specific program consisting of moderate dietary restriction, psychological support, and physical activity. For reference purposes, an additional group of 36 age‐ and gender‐matched healthy‐weight (HW) children was included in the study. Anthropometric measures were recorded and gross motor co‐ordination was assessed using the Körperkoordinationstest für Kinder (KTK) on two occasions with an interval of 4 months. Regardless of the test moment, OW/OB participants displayed significantly poorer KTK performances (P < 0.001). However, treatment was found to be efficacious in decreasing body weight (Δ 17.9 ± 3.1%, P < 0.001) and generating a significant progress in gross motor co‐ordination performance, with a greater increase in KTK score(s) from baseline to re‐test as compared to HW peers (P < 0.01). Within the OW/OB group, the amount of relative weight loss explained 26.9% of the variance in improvement in overall KTK performance. Therefore, multidisciplinary residential treatment and concomitant weight loss can be considered an important means to upgrade OW/OB children's level of gross motor co‐ordination, which in turn may promote physical activity participation.     

Superior Appetite Hormone Profile After Equivalent Weight Loss by Gastric Bypass Compared to Gastric Banding

The goal of this study was to understand the mechanisms of greater weight loss by gastric bypass (GBP) compared to gastric banding (GB) surgery. Obese weight‐ and age‐matched subjects were studied before (T0), after a 12 kg weight loss (T1) by GBP (n = 11) or GB (n = 9), and at 1 year after surgery (T2). peptide YY_3–36 (PYY_3–36), ghrelin, glucagon‐like peptide‐1 (GLP‐1), leptin, and amylin were measured after an oral glucose challenge. At T1, glucose‐stimulated GLP‐1 and PYY levels increased significantly after GBP but not GB. Ghrelin levels did not change significantly after either surgery. In spite of equivalent weight loss, leptin and amylin decreased after GBP, but not after GB. At T2, weight loss was greater after GBP than GB (P = 0.003). GLP‐1, PYY, and amylin levels did not significantly change from T1 to T2; leptin levels continued to decrease after GBP, but not after GB at T2. Surprisingly, ghrelin area under the curve (AUC) increased 1 year after GBP (P = 0.03). These data show that, at equivalent weight loss, favorable GLP‐1 and PYY changes occur after GBP, but not GB, and could explain the difference in weight loss at 1 year. Mechanisms other than weight loss may explain changes of leptin and amylin after GBP.     

The Macrophage‐Specific Serum Marker,Soluble CD163, Is Increased in Obesity and Reduced After Dietary‐Induced Weight Loss

Objective: Soluble CD163 (sCD163) is a new macrophage‐specific serum marker elevated in inflammatory conditions. sCD163 is elevated in obesity and found to be a strong predictor of the development of type 2 diabetes. We investigated whether dietary intervention and moderate exercise was related to changes in sCD163 and how sCD163 is associated to insulin resistance in obesity. Design and Methods: Ninety‐six obese subjects were enrolled: 62 followed a very low energy diet (VLED) program for 8 weeks followed by 3‐4 weeks of weight stabilization, 20 followed a moderate exercise program for 12 weeks, and 14 were included without any intervention. Fasting blood samples and anthropometric measures were taken at baseline and after intervention. Thirty‐six lean subjects were included in a control group. Results: sCD163 was significantly higher in obese subjects (2.3 ± 1.0 mg/l) compared with lean (1.6 ± 0.4 mg/l, P < 0.001). Weight loss (11%) induced by VLED resulted in a reduction and partial normalization of sCD163 to 2.0 ± 0.9 mg/l (P < 0.001). Exercise for 12 weeks had no effect on sCD163. At baseline, sCD163 was significantly correlated with BMI (r = 0.46), waist circumference (r = 0.40), insulin resistance measured by the homeostasis model assessment (HOMA‐IR; r = 0.41; all P < 0.001), and the leptin‐to‐adiponectin ratio (r = 0.28, P < 0.05). In a multivariate linear regression analysis with various inflammatory markers, sCD163 (β = 0.25), adiponectin (β = ?0.24), and high sensitivity C‐reactive protein (hs‐CRP; β = 0.20) remained independently and significantly associated to HOMA‐IR (all P < 0.05). After further adjustment for waist circumference, only sCD163 was associated with HOMA‐IR (P < 0.05). Conclusion: The macrophage‐specific serum marker sCD163 is increased in obesity and partially normalized by dietary‐induced weight loss but not by moderate exercise. Furthermore, we confirm that sCD163 is a good marker for obesity‐related insulin resistance.     

Adolescent Sex Differences in Adiponectin Are Conditional on Pubertal Development and Adiposity

Objective: Adiponectin is an adipose tissue protein with important insulin‐sensitizing, anti‐inflammatory, and cardioprotective properties but is paradoxically lower in obese individuals. Sex differences in adiponectin have been reported in adults and adolescents but not in prepubertal children. In this study, we hypothesized that sex differences in adiponectin would develop during puberty and would be influenced by level of adiposity. Research Methods and Procedures: Adiponectin levels were measured in 1196 white and African‐American adolescents. Insulin resistance was estimated using the homeostasis model (HOMA‐IR). Demographic, developmental, and metabolic variables, including interactions with adiposity measurements, were evaluated for independent relationships with adiponectin levels. Results: Overall, adiponectin levels varied significantly by sex, race, adiposity, and puberty stage. Significant sex differences in adiponectin developed after the onset of puberty, particularly in lean adolescents. Adolescent boys had lower adiponectin levels in post‐puberty compared with pre‐puberty (p = 0.01) and had lower levels than girls in both puberty and post‐puberty (both p < 0.001), after adjusting for race, BMI z‐score, and natural logarithm‐(HOMA‐IR). Sex differences were also conditional on adiposity level, with significant sex differences among lean (p < 0.001) but not among non‐lean (p = 0.16) adolescents. Adiponectin levels in girls decreased more with increasing adiposity than in boys (p = 0.004), but only marginally so after standardizing for girls’ higher mean adiponectin level (p = 0.11). Discussion: Sex differences in adiponectin are dependent on both puberty stage and adiposity in adolescents, such that by post‐puberty, non‐lean boys exhibit the lowest levels of adiponectin.     

Preatherosclerosis and adiponectin subfractions in obese adolescents

We evaluated total adiponectin, high-molecular weight (HMW), medium-molecular weight (MMW), low-molecular weight (LMW) adiponectin subfractions, clinical parameters, routine lab parameters, lipids, metabolic, inflammatory biomarkers, and intima-media thickness (IMT) of common carotid arteries in 70 obese juveniles and adolescents with preatherosclerosis and 55 normal weight controls of similar age and gender distribution. Compared with the controls, the obese probands had a significantly increased IMT (P < 0.001) and elevated ultra-sensitive C-reactive protein (P < 0.001) indicating early vascular burden. Total and HMW adiponectin were significantly decreased in the obese cohort. The ratio between HMW and total adiponectin was significantly decreased in obese probands whereas the LMW/total adiponectin ratio was increased. Overall, total-, HMW, and MMW adiponectin were significantly negatively correlated with carotid IMT. The HMW/total adiponectin ratio correlated significantly negatively, and the LMW/total adiponectin ratio significantly positively with the IMT. Furthermore, HMW adiponectin was significantly positively correlated with high-density lipoprotein (HDL)-cholesterol and serum apolipoprotein A1, and negatively with BMI, triglycerides, homeostatic model assessment (HOMA)-index, leptin, liver transaminases, and uric acid. This remained stable after controlling for gender. Multiple regression analysis of body measures and all other lab parameters showed the strongest correlation between HMW adiponectin and carotid IMT (beta = -0.35, P < 0.001). Taken together, our study provides the first evidence that preatherosclerosis in obese juveniles and adolescents is associated with altered subfractions of adiponectin, whereas after multiple testing the HMW subfraction showed a better correlation to IMT compared with total adiponectin.     

Severely Obese Have Greater LPS‐stimulated TNF‐α Production Than Normal Weight African‐American Women

Obesity is associated with an increase in chronic, low‐grade inflammation which has been implicated in the development of type 2 diabetes mellitus and cardiovascular disease. The purpose of this study was to determine whether obesity was associated with an elevation of whole blood lipopolysaccharide (LPS)‐stimulated tumor necrosis factor‐α (TNF‐α) production. African‐American women were recruited from a larger study and assigned to one of five groups based on BMI: normal weight (NORM; BMI 20–25, n = 7), overweight (OVER; BMI 25–30, n = 12), class 1 obese (OB1; BMI 30–35, n = 19), class 2 obese (OB2; BMI 35–40, n = 10), or class 3 obese (OB3; BMI >40, n = 17). Body composition was determined via a whole body dual‐energy X‐ray absorptiometry (DXA) scan. Venous blood samples were collected following an overnight fast (>8 h), and stimulated with five doses of LPS (Salmonella enteriditis): 80, 40, 20, 10, and 5 µg/ml for 24 h in a 37 °C, 5% CO₂ incubator. Following stimulation, TNF‐α was measured using enzyme‐linked immunosorbent assay. OB3 produced 365% more TNF‐α than NORM at an LPS dose of 20 µg/ml (P < 0.05). When maximal TNF‐α production was assessed regardless of LPS dose, OB3 produced 230% more than NORM and OVER produced 190% more than NW (P = 0.001). Total and trunk fat mass and BMI were significantly correlated with maximal TNF‐α production and LPS = 20 µg/ml. Our findings are consistent with previous reports suggesting a relationship between increased adiposity and inflammatory marker production. This is one of the first studies to focus on African‐American women, who have higher rates of obesity.     

Higher Adiponectin Levels Predict Greater Weight Gain in Healthy Women in the Nurses' Health Study

Adiponectin and resistin's possible roles in weight regulation have received little attention. We tested the hypothesis that adipokine levels predict future weight gain in women in the Nurses' Health Study. Among women who provided blood samples in 1990, we studied 1,063 women who did not develop diabetes (“healthy”) and 984 women who subsequently developed diabetes. Total and high‐molecular‐weight (HMW) adiponectin and resistin levels were measured using enzyme‐linked immunosorbent assay. Women who did not developed diabetes had a mean BMI of 26.3 ± 6.0 kg/m² at baseline and gained 2.0 ± 6.1 kg over 4 years. Women who developed diabetes had a mean BMI of 30.1 ± 5.4 kg/m² at baseline, and gained 2.4 ± 7.1 kg over 4 years. In women who did not developed diabetes, higher baseline levels of total and HMW adiponectin were associated with significantly greater weight gain after adjustment for age, BMI, physical activity, diet, and other covariates: women in the highest quintile of total adiponectin gained 3.18 kg compared to women in the lowest quintile who gained 0.80 kg (fully adjusted; P for trend <0.0001). Adiponectin was not significantly associated with weight gain in women who subsequently developed diabetes. Resistin levels were not associated with weight gain in either women who did or did not develop diabetes during the follow‐up. We conclude that elevated adiponectin levels are associated with higher weight gain in healthy women, independent of confounding risk factors. High adiponectin production by adipocytes might be a sign of “healthy” adipose tissue with further capacity to store fat.     

Adiponectin and leptin in African Americans

Objective: African Americans (AAs) have less visceral and more subcutaneous fat than whites, thus the relationship of adiponectin and leptin to body fat and insulin sensitivity in AA may be different from that in whites. Methods and Procedures: Sixty‐nine non‐diabetic AA (37 men and 32 women), aged 33 ± 1 year participated. The percent fat was determined by dual‐energy X‐ray absorptiometry, abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume by computerized tomography (CT), and insulin sensitivity by homeostasis model assessment (HOMA). Results: VAT was greater in men (1,619 ± 177 cm³ vs. 1,022 ± 149 cm³; P = 0.01); women had a higher percentage of body fat (34.1 ± 1.4 vs. 24.0 ± 1.2; P < 0.0001), adiponectin (15.8 ± 1.2 μg/ml vs. 10.4 ± 0.8 μg/ml; P = 0.0004) and leptin (23.2 ± 15.8 ng/ml vs. 9.2 ± 7.2 ng/ml; P < 0.0001). SAT and HOMA did not differ because of the sex. Adiponectin negatively correlated with VAT (r = ?0.41, P < 0.05) in men, and with VAT (r = ?0.55, P < 0.01), and SAT (r = ?0.35, P < 0.05) in women. Adiponectin negatively correlated with HOMA in men (r = ?0.38, P < 0.05) and women (r = ?0.44, P < 0.05). In multiple regression, sex (P = 0.02), HOMA (P = 0.03) and VAT (P = 0.003) were significant predictors of adiponectin (adj R ² = 0.38, P < 0.0001). Leptin positively correlated with VAT, SAT, percent fat and HOMA in men (r = 0.79, r = 0.86, r = 0.89, and r = 0.53; P < 0.001) and women (r = 0.62, r = 0.75, r = 0.83, and r = 0.55; P < 0.01). In multiple regression VAT (P = 0.04), percent body fat (P < 0.0001) and sex (P = 0.01), but not HOMA were significant predictors of serum leptin (adj R ²= 0.82, P < 0.0001). Discussion: The relationship of adiponectin and leptin to body fat content and distribution in AA is dependent on sex. Although VAT and insulin sensitivity are significant determinants of adiponectin, VAT and percent body fat determine leptin.     

Toward an early marker of metabolic dysfunction: omentin-1 in prepubertal children

Omentin-1 is a recently recognized adipokine primarily originating in visceral adipose tissue. We posited that circulating omentin-1 could be an early marker of metabolic dysfunction. To this end, we examined the associations between circulating omentin-1, body fat (bioelectric impedance), an endocrine-metabolic profile (homeostasis model assessment for insulin resistance (HOMA(IR)), serum lipids, high-molecular-weight (HMW) adiponectin and blood pressure (BP)) and family history of obesity and diabetes in asymptomatic prepubertal children (n = 161; 77 boys and 84 girls; age 7 ± 1 year) with a normal distribution of height and weight. Increased circulating omentin-1 was associated with a poorer metabolic profile, with relatively higher HOMA(IR), fasting triacylglycerol, BP and familial prevalence of diabetes (all P < 0.005 to P < 0.0001), and relatively lower fraction of HMW adiponectin (P < 0.005), whereas no relationship was found with body weight or fat or with family history of obesity. All these associations were independent of age, gender and fat mass. In conclusion, circulating omentin-1 may become a marker of metabolic dysfunction integrating insulin sensitivity, markers of adipose-tissue metabolism and BP as early as in prepubertal childhood.     

Adipocyte Fatty Acid‐binding Protein as a Determinant of Insulin Sensitivity in Morbid‐obese Women

The aim of the study was to evaluate human plasma circulating levels of adipocyte fatty acid‐binding protein (A‐FABP) and its relationship with proinflammatory adipocytokines and insulin resistance in a severely obese cohort, before and 1 year after a surgical gastric bypass. Plasmatic levels of A‐FABP were measured in 77 morbid‐obese women before and 1 year after bariatric surgery. Anthropometrical parameters and body composition by bioelectrical impedance analysis were determined. Circulating levels of soluble tumor necrosis factor receptor 2 (sTNFR2), Interleukin 18 (IL‐18), adiponectin, and high‐sensitive C‐reactive protein (hsCRP) were also analyzed. Insulin resistance by homeostasis model assessment of insulin resistance (HOMA‐IR) index was calculated. After massive weight loss, A‐FABP plasmatic levels decreased significantly [7.6 (8.9) vs. 4.3 (5.1); P < 0,001] but no association with circulating adipokines or proinflammatory cytokines, both at the beginning and at the end of follow‐up, was observed. A decrease in sTNFR2, IL‐18, hsCRP, and an increase in adiponectin levels (P < 0.001 in all cases) were observed after the gastric bypass. HOMA‐IR index improved 1 year after surgery and after multiple regression analysis remained associated with A‐FABP after controlling for confounding variables (β = 0.322, P = 0.014; R² for the model 0.281). In morbid‐obese women, plasma A‐FABP concentrations were dramatically reduced after gastric bypass surgery. After weight loss this protein contributed to HOMA‐IR index independently of proinflammatory/antinflammatory cytokine profile. Further studies are warranted to elucidate the role of A‐FABP in the pathogenesis of insulin resistance in morbid obesity.     

Adipokines,Ghrelin and Obesity‐Associated Insulin Resistance in Nondiabetic Patients with Acute Coronary Syndrome

Altered glucose metabolism negatively modulates outcome in acute coronary syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in the general population and these associations may involve obesity‐related changes in circulating ghrelin and adipokines. We aimed at investigating interactions between BMI, insulin resistance and ACS and their associations with plasma ghrelin and adipokine concentrations. Homeostasis model assessment of insulin resistance (HOMA_IR)‐insulin resistance index, plasma adiponectin, leptin, total (T‐Ghrelin), acylated (Acyl‐Ghrelin), and desacylated ghrelin (Desacyl‐Ghrelin) were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched for age, sex, and BMI. Compared with non‐ACS, ACS patients had similar HOMA_IR and plasma adipokines, but lower T‐ and Desacyl‐Ghrelin and higher Acyl‐Ghrelin. Obesity (BMI > 30) was associated with higher HOMA_IR, lower adiponectin, and higher leptin (P < 0.05) similarly in ACS and non‐ACS subjects. In ACS (n = 60) HOMA_IR remained associated negatively with adiponectin and positively with leptin independently of BMI and c‐reactive protein (CRP) (P < 0.05). On the other hand, low T‐ and Desacyl‐Ghrelin with high Acyl‐Ghrelin characterized both obese and non‐obese ACS patients and were not associated with HOMA_IR. In conclusion, in ACS patients, obesity and obesity‐related changes in plasma leptin and adiponectin are associated with and likely contribute to negatively modulate insulin resistance. ACS per se does not however enhance the negative impact of obesity on insulin sensitivity. High acylated and low desacylated ghrelin characterize ACS patients independently of obesity, but are not associated with insulin sensitivity.