Novel associations between bioavailable estradiol and adipokines in elderly women with different phenotypes of obesity. Implications for atherogenesis

• Published in: Circulation (New York, N.Y.) Vol. 110; no. 15; pp. 2246 - 2252
• Main Authors: TANKO, Laszlo B, BRUUN, Jens M, ALEXANDERSEN, Peter, BAGGER, Yu Z, RICHELSEN, Bjørn, CHRISTIANSEN, Claus, LARSEN, Philip J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 12-10-2004
• Subjects: Absorptiometry, Photon; Adiponectin; Aged; Anthropometry; Aortic Diseases - diagnostic imaging; Aortic Diseases - etiology; Arteriosclerosis - etiology; Biological and medical sciences; Blood and lymphatic vessels; Calcinosis - diagnostic imaging; Calcinosis - etiology; Cardiology. Vascular system; Cytokines - blood; Dermatology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Estradiol - blood; Female; Fundamental and applied biological sciences. Psychology; General aspects; Humans; Hyperlipidemias - complications; Hypertension - complications; Insulin Resistance; Intercellular Signaling Peptides and Proteins - blood; Interleukin-6 - blood; Medical sciences; Obesity - classification; Obesity - complications; Obesity - diagnostic imaging; Obesity - metabolism; Phenotype; Risk Factors; Sex Hormone-Binding Globulin - analysis; Skin involvement in other diseases. Miscellaneous. General aspects; Smoking - epidemiology; Tumor Necrosis Factor-alpha - analysis; Vertebrates: cardiovascular system; Human; Obesity; insulin; hormones; Estrogen; Nutrition disorder; Cardiovascular disease; Estradiol; Ovarian hormone; Vascular disease; Phenotype; Atherosclerosis; aging; Sex steroid hormone; Elderly; Nutritional status
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000144470.55149.E5

Peripheral adiposity confers protection against diabetes and atherosclerosis in elderly women. The underlying mechanisms, however, remain to be elucidated.
On the basis on dual-energy X-ray absorptiometry measurements of central fat mass (CFM) and peripheral fat mass (PFM), we identified 290 elderly women with distinct forms of body fat distribution (lean, peripheral obesity, central obesity, or general obesity). Study parameters were plasma tumor necrosis factor-alpha, interleukin (IL)-6, adiponectin, estradiol, sex hormone-binding globulin, insulin resistance, and aortic calcification, graded on lateral radiography. In peripherally and generally obese women, plasma estradiol and insulin resistance were significantly lower, whereas sex hormone-binding globulin and adiponectin were significantly higher compared with centrally obese women independent of age, body mass index, total fat mass, and smoking habits (all P<0.05). After adjustment for these confounders, IL-6 in centrally obese women was comparable with that seen in generally obese (similar high CFM%) but significantly higher than in peripherally obese women and lean women (low CFM%). Atherosclerosis was less severe in generally obese (2.5+/-0.3) compared with centrally obese women (5.0+/-0.7, P=0.001). In multiple regression analysis, total fat mass, body fat distribution, insulin resistance, estradiol, current smoking, treated hyperlipidemia, and treated hypertension contributed independently to the variation of aortic calcification (R=0.55, SEE=3.60, P<0.001).
Abundant presence of PFM in generally obese women is associated with increased plasma adiponectin and higher insulin sensitivity, which could explain the apparent protection against the atherogenic effects of IL-6 derived from CFM. Low peripheral exposure to estradiol appears to be a sine qua non of maintained adiponectin secretion from PFM.