Adiponectin as an anti-inflammatory factor

doi:10.1016/j.cca.2007.01.026

Clinica Chimica Acta

Volume 380, Issues 1–2, 1 May 2007, Pages 24-30

https://doi.org/10.1016/j.cca.2007.01.026 Get rights and content

Abstract

Obesity is characterized by low-grade systemic inflammation. Adiponectin is an adipose tissue-derived hormone, which is downregulated in obesity. Adiponectin displays protective actions on the development of various obesity-linked diseases. Several clinical studies demonstrate the inverse relationship between plasma adiponectin levels and several inflammatory markers including C-reactive protein. Adiponectin attenuates inflammatory responses to multiple stimuli by modulating signaling pathways in a variety of cell types. The anti-inflammatory properties of adiponectin may be a major component of its beneficial effects on cardiovascular and metabolic disorders including atherosclerosis and insulin resistance. In this review, we focus on the role of adiponectin in regulation of inflammatory response and discuss its potential as an anti-inflammatory marker.

Introduction

Increasing evidence indicates that chronic mild inflammation linked to obesity is closely associated with the development of insulin resistance and cardiovascular disorders [1]. A number of bioactive substances secreted from fat tissue, referred to as adipokines, could contribute to the complications of obesity through the regulation of inflammatory and immune responses [2], [3]. Adipokines include pro-inflammatory cytokines/chemokines such as leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) [2], [3]. In contrast, the adipokine adiponectin exerts anti-inflammatory actions on a number of cell types.

Adiponectin, also referred to as ACRP30, AdipoQ and gelatin-binding protein-28 [4], [5], [6], is expressed almost exclusively in adipose tissue [5], [6]. Adiponectin is abundantly present in blood stream, and the average levels of plasma adiponectin in human range 3 to 30 μg/ml [2], [7]. Adiponectin is a 244-amino acid protein that contains a putative signal sequence and a collagen-like domain followed by a globular domain similar to collagens VIII and X and compliment factor C1q. Of importance, plasma adiponectin levels are paradoxically decreased in obese subjects [7]. Low plasma adiponectin levels, known as hypoadiponectinemia, are closely associated with obesity-linked complications including type 2 diabetes, coronary heart disease and hypertension. A number of experimental studies suggest that adiponectin can act as a protective factor against insulin resistance and cardiovascular disease. In this review, we focus on the possible role of adiponectin in obesity-associated inflammatory states.

Section snippets

Atherosclerosis

Atherosclerosis is characterized by chronic systemic inflammation. Endothelial cell activation by pro-inflammatory stimuli and subsequent monocyte adherent to injured endothelium is a precipitating event in atherogenesis [8]. Adiponectin treatment reduces TNF-α-stimulated expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, intracellular adhesion molecule-1 and IL-8 in human aortic endothelial cells as well as monocyte attachment to TNF-α-stimulated endothelial cells (Fig. 1)

Obesity-linked metabolic disorders

Numerous epidemiological studies emphasized the association between adiponectin levels and obesity-linked conditions. Plasma adiponectin levels are significantly lower in obese subjects compared with non-obese subjects [7]. This inverse correlation is observed between plasma adiponectin concentrations and body mass index (BMI) in both genders [7]. In addition, plasma adiponectin levels negatively correlate with visceral fat accumulation in both men and women [63].

Several clinical studies

Regulation of adiponectin

As mentioned above, obesity promotes hypoadiponectinemia. It is believed that chronic inflammation associated with excess adiposity is a key feature of adiponectin downregulation under these conditions. Pro-inflammatory cytokines suppress adiponectin expression in adipocytes. TNF-α treatment suppresses adiponectin expression at the level of transcription in cultured 3T3-L1 adipocytes [94] and reduces the expression and secretion of adiponectin protein in primary human adipocytes [95].

Conclusion

Adiponectin can function as a modulator of multiple obesity-linked diseases by attenuating excessive inflammatory responses in a variety of tissues. While putative adiponectin receptors are expressed in various cells and tissues where adiponectin exerts anti-inflammatory actions, their involvement in adiponectin-mediated suppression of cellular inflammatory responses has not been definitely established. In contrast, the receptor-mediated signaling events that control metabolic processes

Acknowledgements

This work was supported by NIH grants HL66957, HL77774, AR40197 and AG15052 to K. Walsh. N. Ouchi was supported by an American Heart Association Scientist Development Grant, Northeast Affiliate.

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Invited critical reviewAdiponectin as an anti-inflammatory factor

Abstract

Introduction

Section snippets

Atherosclerosis

Obesity-linked metabolic disorders

Regulation of adiponectin

Conclusion

Acknowledgements

J Biol Chem

Biochem Biophys Res Commun

J Biol Chem

Biochem Biophys Res Commun

Blood

Biochem Biophys Res Commun

FEBS Lett

Diabetes Res Clin Pract

J Biol Chem

Am Heart J

J Am Coll Cardiol

J Biol Chem

J Biol Chem

Biochem Biophys Res Commun

Biochem Biophys Res Commun

J Biol Chem

FEBS Lett

J Mol Cell Cardiol

Am Heart J

J Biol Chem

J Biol Chem

J Biol Chem

Lancet

Lancet

Am J Hypertens

J Am Coll Cardiol

Atherosclerosis

Biochem Biophys Res Commun

Obesity-induced inflammatory changes in adipose tissue

J Clin Invest

Obesity, adiponectin and vascular inflammatory disease

Curr Opin Lipidol

Adipose tissue, inflammation, and cardiovascular disease

Circ Res

Atherosclerosis

Nature

Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin

Circulation

Adiponectin inhibits endothelial synthesis of interleukin-8

Circ Res

Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway

Circulation

Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway

Diabetes

Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages

Circulation

Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages

Circulation

Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice

Circulation

Impaired collateral vessel development in diabetes: potential cellular mechanisms and therapeutic implications

Cardiovasc Res

Capillary surface area is reduced and tissue thickness from capillaries to myocytes is increased in the left ventricle of streptozotocin-diabetic rats

Diabetologia

Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure

J Clin Invest

Obesity is associated with impaired coronary collateral vessel development

Int J Obes Relat Metab Disord

Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance

J Clin Invest

Globular adiponectin upregulates nitric oxide production in vascular endothelial cells

Diabetologia

Nitric oxide: physiology, pathophysiology and pharmacology

Pharmacol Rev

Adiponectin replenishment ameliorates obesity-related hypertension

Hypertension

Association of hypoadiponectinemia with impaired vasoreactivity

Hypertension

Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin

Circ Res

Adiponectin protects against myocardial ischemia–reperfusion injury through AMPK- and COX-2-dependent mechanisms

Invited critical review
Adiponectin as an anti-inflammatory factor