Globular Adiponectin Activates Nuclear Factor–κB in Vascular Endothelial Cells, Which in Turn Induces Expression of Proinflammatory and Adhesion Molecule Genes
- Yoshiyuki Hattori, MD, PHD,
- Sachiko Hattori, MD, PHD and
- Kikuo Kasai, MD, PHD
- From the Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Japan
- Address correspondence and reprint requests to Yoshiyuki Hattori, MD, PhD, Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, 321-0293, Japan. E-mail: yhattori{at}dokkyomed.ac.jp
- HMW, high molecular weight
- HUVEC, human umbilical vein endothelial cell
- NF-κB, nuclear factor κB
- TNF, tumor necrosis factor
Adiponectin is present in serum in trimer, hexamer, or high–molecular weight (HMW) form. A proteolytic cleavage product of adiponectin, known as globular adiponectin, has also been found to circulate in human plasma (1). The biological activities of these isoforms is controversial. It has been shown that recombinant globular adiponectin is pharmacologically active and induces free fatty acid oxidation in incubated mouse muscle and cultured muscle cells (1). Yamauchi et al. (2) have reported significantly greater potency of globular adiponectin in reversing insulin resistance than uncleaved adiponectin. However, it has recently been proposed that the ratio of HMW to total adiponectin, but not the absolute amounts of adiponectin, determines insulin sensitivity in humans and rodents (3). Clinical data also confirmed that patients with type 2 diabetes and coronary heart diseases have a selective reduction in HMW adiponectin (3,4). The experimental and clinical data collectively suggest that the oligomeric complex distribution of adiponectin is critical for the antidiabetes and antiatherogenic activity of this hormone (4).
RESEARCH DESIGN AND METHODS
We thus questioned how globular adiponectin alters the gene expression in human umbilical vein endothelial cells (HUVECs). First, we confirmed the adiponectin receptor 1 gene expression in HUVECs, which have a high …
