Clinical Science (2008) 114, 275-288 - H. Tilg and A.R. Moschen - Adiponectin and PBEF/visfatin as regulators of inflammation

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Clinical Science (2008) 114, (275–288) (Printed in Great Britain)

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Review article

Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases

Herbert TILG and Alexander R. MOSCHEN

Christian Doppler Research Laboratory for Gut Inflammation, Department of Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria

Key words: adiponectin, inflammation, insulin resistance, obesity, pre-B-cell-enhancing factor (PBEF), visfatin.

Abbreviations: AMPK, AMP-activated protein kinase; BAT, brown adipose tissue; BMI, body mass index; CCL-2, CC chemokine ligand-2; CRP, C-reactive protein; DC, dendritic cell; DSS, dextran sulphate sodium; HMW, high-molecular-weight (‘mass’); IBD, inflammatory bowel disease; IFN-g, interferon-g; IL, interleukin; IL-1Ra, IL-1 receptor antagonist; IR, insulin resistance; JNK, c-Jun N-terminal kinase; LMW, low-molecular-weight (‘mass’); LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein-1; MMW, middle-molecular-weight (‘mass’); NASH, non-alcoholic steatohepatitis; NF-kB, nuclear factor kB; NK, natural killer; PPAR, peroxisome-proliferator-activated receptor; PBEF, pre-B-cell-enhancing factor; RANTES, regulated upon activation, normal T-cell expressed and secreted; RPB-4, retinol-binding protein-4; T2DM, Type 2 diabetes mellitus; TLR, Toll-like receptor; TNF, tumour necrosis factor; T_reg-cell, regulatory T-cell; WAT, white adipose tissue.

Obesity and obesity-related disorders play an important role in clinical medicine. Adipose tissue, with its soluble mediators called adipocytokines, has emerged as a major endocrine organ. These adipocytokines comprise many mediators such as adiponectin, PBEF (pre-B-cell-enhancing factor)/visfatin, leptin, resistin, retinol-binding protein-4 and others. They play major roles in key aspects of metabolism, such as insulin resistance, fatty acid oxidation, inflammation and immunity. Adiponectin, a prototypic adipocytokine, is of importance in the regulation of insulin resistance, as circulating levels are decreased in obesity and diseases associated with insulin resistance. Besides its major role in regulation of insulin sensitivity, recent evidence suggests potent anti-inflammatory functions for adiponectin. These effects are paralleled by other immune-regulatory properties, such as regulation of endothelial cell function. The in vitro effects of adiponectin have been corroborated by several studies demonstrating potent in vivo anti-inflammatory effects. Many other adipocytokines, such as PBEF/visfatin, leptin, resistin or retinol binding protein-4, are involved in the physiology and pathophysiology of adipocytes, adipose tissue and related diseases. PBEF/visfatin, another recently characterized adipocytokine, has been linked to several inflammatory disease states beyond insulin resistance, such as acute lung injury or inflammatory bowel diseases. It has been recognized for many decades that obesity is accompanied by an increase in cancer and potentially some immune-mediated diseases. Understanding this new exciting world of adipocytokines will be of importance in the development of novel therapies for obesity-associated diseases.