Review and feature article
Adipose tissue, adipokines, and inflammation

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White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-α, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.

Section snippets

Obesity, adipose tissue, and inflammation

The incidence of obesity and associated comorbidities is dramatically increasing worldwide in both children and adults. The obese state is characterized by what has been called low-grade systemic inflammation. In fact, inflammatory markers, such as C-reactive protein (CRP) and IL-6, are increased in obese individuals compared with lean subjects, although not to the same extent observed in classic inflammatory conditions. The presence of systemic inflammation has been linked to the increased

Macrophages are present in adipose tissue and increased in obesity

Adipose tissue can be divided into 2 major types: white adipose tissue (WAT) and brown adipose tissue. WAT represents the vast majority of adipose tissue in the organism and is the site of energy storage, whereas the main role of brown adipose tissue is nonshivering thermogenesis, particularly in small mammals and human neonates. WAT is composed of many cell types, adipocytes being the most abundant. The other cell types present in WAT are included in the stromovascular fraction, of which

Adipokines

Adipokines are proteins produced mainly by adipocytes. Although adipose tissue secretes a variety of factors, only leptin and adiponectin (and possibly resistin, adipsin, and visfatin) are primarily produced by adipocytes and can therefore be properly classified as adipokines.

IL-6 and TNF-α

IL-6 and TNF-α are the 2 best-studied cytokines in obesity and have been consistently found to be increased in the serum, WAT, or both of obese subjects.8

It has been estimated that WAT contributes about 30% of circulating IL-6, with visceral WAT producing higher levels of IL-6 compared with subcutaneous WAT.53, 54 Both adipocytes and macrophages contribute to WAT-derived IL-6, although the ultimate stimulus for induction of IL-6 production in the presence of excess adiposity is currently

Correlation between adiposity and immunity-inflammation

Obesity, particularly visceral adiposity, is associated with chronic low-grade inflammation, as indicated by increased levels of the inflammatory markers CRP and IL-6 in the circulation of obese subjects. Although not completely demonstrated, the current working hypothesis is that adipokines, cytokines, and other factors produced and released by WAT are responsible for the chronic inflammatory state of visceral obesity. The concomitance of inflammation, hypertension, and dyslipidemia increases

Inflammatory-autoimmune disorders and adipokines

Altered systemic adipokine levels, local adipokine levels, or both have been reported in a variety of inflammatory-autoimmune conditions, with the majority of studies focusing on leptin. However, the pathogenic role played by adipokines in such disorders is far from understood, even for type II diabetes, a disease in which a potential role for adipokines has been studied in more detail. Below we summarize the data available for those conditions in which adipokine levels have been studied in

Conclusions

The recent interest in WAT as an active secretory organ and the observation of close links and similarities between adipocytes and immune-inflammatory cells have generated a sizeable amount of exciting data that have revolutionized our understanding of the role of WAT in physiologic and pathologic processes (Table I). However, the field is still too young to allow for therapeutic implications to be drawn at this point because we still need to understand most of the details regarding adipokine

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    Series editors: William T. Shearer, MD, PhD, Lanny J. Rosenwasser, MD, and Bruce S. Bochner, MD

    Supported by National Institutes of Health grant DK-061483.

    Disclosure of potential conflict of interest: G. Fantuzzi—none disclosed.

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