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      Relatively high levels of serum adiponectin in obese women, a potential indicator of anti-inflammatory dysfunction: Relation to sex hormone-binding globulin

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          Abstract

          It is unclear whether serum adiponectin concentrations diminish linearly with increasing adiposity and, if not, which factors codetermine this association. These issues were investigated cross-sectionally in 1188 men and women, representative of middle-aged and elderly Turkish adults. Serum total adiponectin was assayed by ELISA. Serum adiponectin values in men, though declining significantly in transition from the bottom to the mid tertile of body mass index (BMI) and waist circumference (WC), were similar in the two respective upper tertiles. In women, serum adiponectin concentrations were not significantly different in any tertile of these indices, were significantly correlated with BMI or WC within the low tertiles and not within the two higher tertiles. In a linear regression analysis for WC (or BMI) in a subset of the sample in which serum sex hormone-binding globulin (SHBG) was available and which additionally comprised adiponectin, fasting insulin and other confounders, only insulin and, in women SHBG, were significantly associated, but not adiponectin. In linear regression analyses for covariates of adiponectin in two models comprising 12 variables, insulin and SHBG concentrations were significantly associated in both genders though not BMI. Whereas in men HDL-cholesterol and CRP were covariates of adiponectin (both p<0.01), SHBG and apolipoprotein B positively associated in women (p<0.001), independent of BMI and fasting insulin levels.

          Conclusions: Relationship between excess adiposity and adiponectin levels is inconsistent in Turkish adults. Independently from obesity and hyperinsulinemia, serum adiponectin discloses significant relationship with inflammatory markers and HDL only in men, not in women in whom it is influenced by SHBG, with consequent attenuation of its anti-inflammatory activities.

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          Most cited references26

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          Plasma adiponectin levels and risk of myocardial infarction in men.

          Adiponectin, a recently discovered adipocyte-derived peptide, is involved in the regulation of insulin sensitivity and lipid oxidation and, purportedly, in the development of atherosclerosis and coronary heart disease in humans. To assess prospectively whether plasma adiponectin concentrations are associated with risk of myocardial infarction (MI). Nested case-control study among 18 225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw (1993-1995). During 6 years of follow-up through January 31, 2000, 266 men subsequently developed nonfatal MI or fatal coronary heart disease. Using risk set sampling, controls were selected in a 2:1 ratio matched for age, date of blood draw, and smoking status (n = 532). Incidence of nonfatal MI and fatal coronary heart disease by adiponectin level. After adjustment for matched variables, participants in the highest compared with the lowest quintile of adiponectin levels had a significantly decreased risk of MI (relative risk [RR], 0.39; 95% confidence interval [CI], 0.23-0.64; P for trend <.001). Additional adjustment for family history of MI, body mass index, alcohol consumption, physical activity, and history of diabetes and hypertension did not substantively affect this relationship (RR, 0.41; 95% CI, 0.24-0.70; P for trend <.001). Further adjustment for hemoglobin A1c or C-reactive protein levels also had little impact, but additional adjustment for low- and high-density lipoprotein cholesterol levels modestly attenuated this association (RR, 0.56; 95% CI, 0.32-0.99; P for trend =.02). High plasma adiponectin concentrations are associated with lower risk of MI in men. This relationship can be only partly explained by differences in blood lipids and is independent of inflammation and glycemic status.
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            Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein.

            Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 +/- 11.9 years [mean +/- SD]) than in 137 women (53.2 +/- 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.
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              Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure.

              Recent studies have suggested that higher body mass index (BMI) is associated with improved prognosis in chronic heart failure (CHF). The adipocytokine adiponectin is inversely associated with BMI, and in healthy subjects, low adiponectin is a predictor of mortality. In a prospective study, we therefore evaluated the association between plasma adiponectin levels and mortality among patients with CHF. In 195 CHF patients (age 69.3+/-10.2 years, BMI 27.3+/-5.2 kg/m2, left ventricular ejection fraction 30+/-8.9%, mean+/-SD), plasma adiponectin and N-terminal pro brain natriuretic peptide (NT-proBNP) were measured at baseline. Adiponectin was positively associated with NT-proBNP (beta=0.47, P<0.001), and both biomarkers were negatively associated with BMI (beta=-0.43, P<0.001 for adiponectin and beta=-0.38, P<0.001 for NT-proBNP, respectively) During a median follow-up of 2.6 years, 46 (23.5%) of the patients died. After adjustment for clinical variables associated with CHF severity (age, systolic blood pressure, left ventricular ejection fraction <25%, duration of CHF, and creatinine clearance) and for NT-proBNP, the hazard ratio of mortality for values in the 2 upper tertiles relative to the lowest tertile of adiponectin was 3.23 (P=0.032). BMI predicted mortality independently of clinical parameters of CHF severity (hazard ratio=0.63, P=0.012), but this association became insignificant after additional adjustment for NT-proBNP (hazard ratio=0.74, P=0.13). A high adiponectin level was a predictor of mortality, independent of risk markers of CHF severity, presumably because of its role as a marker for wasting. BMI was also associated with mortality, but a part of this relation may be mediated by adiponectin and NT-proBNP levels.
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                Author and article information

                Journal
                Int J Biol Sci
                ijbs
                International Journal of Biological Sciences
                Ivyspring International Publisher (Sydney )
                1449-2288
                2008
                25 July 2008
                : 4
                : 4
                : 208-214
                Affiliations
                1. Turkish Society of Cardiology, Istanbul University, İstanbul, Turkey
                2. Departments of Cardiology and Public Health, Cerrahpaşa Medical Faculty, Istanbul University, İstanbul, Turkey
                3. Biology Department, Yıldız Technical University, İstanbul, Turkey
                4. Department of Cardiology, Pamukkale University Medical Faculty, Denizli, Turkey
                5. Department of Cardiology, Gaziantep University Medical Faculty, Gaziantep, Turkey
                6. Department of Cardiology, Düzce University Medical Faculty, Düzce, Turkey
                Author notes
                Correspondence to: Prof.Dr. Altan Onat, Nisbetiye cad. 37/24, Etiler 34335, İstanbul, Turkey. Tel. 90 212 351 6217, Fax 90 212 351 4235, E-mail: alt_onat@ 123456yahoo.com.tr

                Conflict of Interest: The authors have declared that no conflict of interest exists.

                Article
                ijbsv04p0208
                2491727
                18695734
                5640a644-961b-4aad-8168-8a00385e1d66
                © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                : 13 June 2008
                : 19 July 2008
                Categories
                Research Paper

                Life sciences
                adiponectin,sex hormone-binding globulin,gender difference,obesity,anti-inflammatory function,waist circumference

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