Obesity, adiponectin and vascular inflammatory disease.
OBJECTIVE
Obesity is the most common risk factor for cardiovascular diseases in industrial countries. It is now clear that adipose tissue secretes various bioactive substances, conceptualized as adipocytokines, and that dysregulation of adipocytokines directly contributes to obesity-related diseases. Chronic inflammatory processes contribute to the development of atherosclerosis. In this review, the authors focus on the relationship between adiponectin, a recently discovered anti-atherogenic adipocytokine, and vascular inflammation.


RESULTS
Plasma concentrations of adiponectin, an adipocyte-specific protein, are reduced in obese subjects and in patients with type 2 diabetes and coronary artery disease. Adiponectin inhibits the expression of tumor necrosis factor-alpha-induced endothelial adhesion molecules, macrophage-to-foam cell transformation, tumor necrosis factor-alpha expression in macrophages and adipose tissues, and smooth muscle cell proliferation. In addition, adenovirus-expressed adiponectin reduces atherosclerotic lesions in a mouse model of atherosclerosis, and adiponectin-deficient mice exhibit an excessive vascular remodeling response to injury. Clinically, hypoadiponectinemia is closely associated with increased levels of inflammatory markers such as C-reactive protein and interleukin-6.


CONCLUSIONS
Adiponectin acts as an anti-inflammatory and anti-atherogenic plasma protein. Adiponectin is an endogenous biologically relevant modulator of vascular remodeling linking obesity and vascular disease.
Ouchi
Noriyuki
N
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. ouchi@imed2.med.osaka-u.ac.jp
Kihara
Shinji
S
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
Walsh
Kenneth
K
D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein