Association Between Adiponectin and Mediators of Inflammation
Association Between Adiponectin and Mediators of Inflammation
Low plasma levels of the anti-inflammatory factor adiponectin characterize obesity and insulin resistance. To elucidate the relationship between plasma levels of adiponectin, adiponectin gene expression in adipose tissue, and markers of inflammation, we obtained blood samples, anthropometric measures, and subcutaneous adipose tissue samples from 65 postmenopausal healthy women. Adiponectin plasma levels and adipose-tissue gene expression were significantly lower in obese subjects and inversely correlated with obesity-associated variables, including high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Despite adjustment for obesity-associated variables, plasma levels of adiponectin were significantly correlated to adiponectin gene expression (partial r = 0.38, P < 0.05). Furthermore, the inverse correlation between plasma levels of hs-CRP and plasma adiponectin remained significant despite correction for obesity-associated variables (partial r = -0.32, P < 0.05), whereas the inverse correlation between adiponectin plasma levels or adiponectin gene expression in adipose tissue with plasma IL-6 were largely dependent on the clustering of obesity-associated variables. In conclusion, our data suggest a transcriptional mechanism leading to decreased adiponectin plasma levels in obese women and demonstrate that low levels of adiponectin are associated with higher levels of hs-CRP and IL-6, two inflammatory mediators and markers of increased cardiovascular risk.
Adipocytes are a rich source of molecules that modulate cardiovascular and metabolic risk. The recently identified hydrophilic protein adiponectin, also known as Acrp30, AdipQ, apM1, and GBP28, is exclusively produced by adipocytes and has high homology to complement factor C1q. Plasma adiponectin levels are decreased in obesity, insulin resistance, type 2 diabetes, and dyslipidemia and are particularly low in patients with coronary artery disease. Conversely, weight loss and pharmacological improvement of insulin sensitivity by thiazolidinediones are associated with increased adiponectin levels. Lack of adiponectin resulted in increased susceptibility to diet-induced insulin resistance, and treatment of animals with adiponectin improved insulin resistance and other metabolic abnormalities associated with obesity and lipoatrophy. In vitro, adiponectin suppressed adhesion molecule expression on endothelial cells, reduced vascular inflammatory responses by inhibition of endothelial cell nuclear factor (NF)-
B signaling, and suppressed macrophage function. In vivo, adiponectin adhered to endothelial lesions and prevented neointimal formation and atherosclerosis in mice. In contrast to other adipocyte-derived molecules, adiponectin thus seems to have protective metabolic and anti-inflammatory properties. As little is known about adiponectin regulation, we tested the hypothesis that decreased adiponectin levels in obesity are determined by adiponectin gene expression in human adipose tissue. Furthermore, we examined the relationship between decreased adiponectin levels and interleukin-6 (IL-6), tumor necrosis factor-
(TNF-
), and high-sensitive C-reactive protein (hs-CRP) as mediators of inflammation and markers of cardiovascular risk in nondiabetic postmenopausal women.
Low plasma levels of the anti-inflammatory factor adiponectin characterize obesity and insulin resistance. To elucidate the relationship between plasma levels of adiponectin, adiponectin gene expression in adipose tissue, and markers of inflammation, we obtained blood samples, anthropometric measures, and subcutaneous adipose tissue samples from 65 postmenopausal healthy women. Adiponectin plasma levels and adipose-tissue gene expression were significantly lower in obese subjects and inversely correlated with obesity-associated variables, including high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Despite adjustment for obesity-associated variables, plasma levels of adiponectin were significantly correlated to adiponectin gene expression (partial r = 0.38, P < 0.05). Furthermore, the inverse correlation between plasma levels of hs-CRP and plasma adiponectin remained significant despite correction for obesity-associated variables (partial r = -0.32, P < 0.05), whereas the inverse correlation between adiponectin plasma levels or adiponectin gene expression in adipose tissue with plasma IL-6 were largely dependent on the clustering of obesity-associated variables. In conclusion, our data suggest a transcriptional mechanism leading to decreased adiponectin plasma levels in obese women and demonstrate that low levels of adiponectin are associated with higher levels of hs-CRP and IL-6, two inflammatory mediators and markers of increased cardiovascular risk.
Adipocytes are a rich source of molecules that modulate cardiovascular and metabolic risk. The recently identified hydrophilic protein adiponectin, also known as Acrp30, AdipQ, apM1, and GBP28, is exclusively produced by adipocytes and has high homology to complement factor C1q. Plasma adiponectin levels are decreased in obesity, insulin resistance, type 2 diabetes, and dyslipidemia and are particularly low in patients with coronary artery disease. Conversely, weight loss and pharmacological improvement of insulin sensitivity by thiazolidinediones are associated with increased adiponectin levels. Lack of adiponectin resulted in increased susceptibility to diet-induced insulin resistance, and treatment of animals with adiponectin improved insulin resistance and other metabolic abnormalities associated with obesity and lipoatrophy. In vitro, adiponectin suppressed adhesion molecule expression on endothelial cells, reduced vascular inflammatory responses by inhibition of endothelial cell nuclear factor (NF)-
B signaling, and suppressed macrophage function. In vivo, adiponectin adhered to endothelial lesions and prevented neointimal formation and atherosclerosis in mice. In contrast to other adipocyte-derived molecules, adiponectin thus seems to have protective metabolic and anti-inflammatory properties. As little is known about adiponectin regulation, we tested the hypothesis that decreased adiponectin levels in obesity are determined by adiponectin gene expression in human adipose tissue. Furthermore, we examined the relationship between decreased adiponectin levels and interleukin-6 (IL-6), tumor necrosis factor-
(TNF-
), and high-sensitive C-reactive protein (hs-CRP) as mediators of inflammation and markers of cardiovascular risk in nondiabetic postmenopausal women.