Monocyte chemoattractant protein-1 secreted by adipose tissue induces direct lipid accumulation in hepatocytes.

Unlabelled: For many years, adipose tissue has been mainly considered as an inert reservoir for storing triglycerides. Since the discovery that adipocytes may secrete a variety of bioactive molecules (hormones, chemokines, and cytokines), an endocrine and paracrine role for white adipose tissue (WAT) in the regulation of energy balance and other physiological processes has been established, particularly with regard to brain and muscle. In contrast, little is known about the interactions of WAT with liver.

Explant cultures of white adipose tissue.

Obesity is characterized by increased adiposity of visceral and subcutaneous depots as well as other organs, including the vasculature. These fat depots secrete various hormone-like proteins implicated in metabolic homeostasis (e.g.

Adipose tissue has anti-inflammatory properties: focus on IL-1 receptor antagonist (IL-1Ra).

The formation of adipose tissue could result from abnormal metabolic processes and, at the local level, from chronic inflammatory processes such as those occurring in the synovial cavity in rheumatoid arthritis or osteoarthritis, or the peritoneal cavity in various inflammatory processes of the digestive system. Adipocytes are said to produce many hormones and proinflammatory mediators. So far, however, little attention has been paid to cytokine inhibitory molecules.

Adipose tissue: a regulator of inflammation.

Adipose tissue is a highly active organ. In addition to storing calories as triglycerides, it also secretes a large variety of proteins, including cytokines, chemokines and hormone-like factors, such as leptin, adiponectin and resistin. Intriguingly, many, if not most, of these adipose-derived proteins have dual actions; cytokines have both immunomodulatory functions and act as systemic or auto-/paracrine regulators of metabolism, while proteins such as leptin and adiponectin are regulators of both metabolism and inflammation.

Decreased fat mass in interleukin-1 receptor antagonist-deficient mice: impact on adipogenesis, food intake, and energy expenditure.

Interleukin (IL)-1 is a regulator of inflammation but is also implicated in the control of energy homeostasis. Because the soluble IL-1 receptor antagonist (IL-1Ra) is markedly increased in the serum of obese patients and is overexpressed in white adipose tissue in obesity, we studied the metabolic consequences of genetic IL-1Ra ablation in mice. We have shown that IL-1Ra-/- mice have a lean phenotype due to decreased fat mass, related to a defect in adipogenesis and increased energy expenditure.

Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis?

Objective: Obesity is associated with an increased risk for cardiovascular disease. Although it is known that white adipose tissue (WAT) produces numerous proinflammatory and proatherogenic cytokines and chemokines, it is unclear whether adipose-derived chemotactic signals affect the chronic inflammation in atherosclerosis.

Methods And Results: Histological examination showed that perivascular WAT (pWAT) is in close proximity to vascular walls, particularly at sites that have a tendency to develop atherosclerosis.

Adipose tissue is a regulated source of interleukin-10.

White adipose tissue (WAT) is the source of pro- and anti-inflammatory cytokines and we have recently shown that this tissue is a major source of the anti-inflammatory interleukin (IL)-1 receptor antagonist (IL-1Ra). We now aimed at identifying additional adipose-derived cytokines, which might serve as regulators of IL-1Ra. We demonstrate here for the first time that the antiinflammatory cytokine IL-10 is secreted by human WAT explants and that it is up-regulated by LPS and TNF-alpha in vitro, as well as in obesity in humans (2- and 6-fold increase in subcutaneous and visceral WAT, respectively) and rodents (4-fold increase).

Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue.

Adipose tissue is the source of production and site of action of several pro- and antiinflammatory cytokines. We have recently shown that white adipose tissue (WAT) is a major producer of the antiinflammatory IL-1 receptor antagonist (IL-1Ra). Because IL-1Ra serum levels are elevated 7-fold in human obesity and an excess of this protein has been implicated in the acquired resistance to leptin and insulin, we investigated the regulation of IL-1Ra in human WAT.

Adipose tissue is a major source of interleukin-1 receptor antagonist: upregulation in obesity and inflammation.

The secreted form of the interleukin-1 receptor antagonist (IL-1Ra) is an acute-phase protein intervening in the counterregulation of inflammatory processes. We previously showed that this cytokine antagonist is upregulated in the serum of obese patients, correlating with BMI and insulin resistance. In this study, we examined the expression pattern of IL-1Ra and showed that it is highly expressed not only in liver and spleen, but also in white adipose tissue (WAT), where it is upregulated in obesity.

Leptin activates the promoter of the interleukin-1 receptor antagonist through p42/44 mitogen-activated protein kinase and a composite nuclear factor kappa B/PU.1 binding site.

We have recently shown that leptin strongly induces the expression and secretion of the interleukin-1 receptor antagonist (IL-1Ra) [Gabay, Dreyer, Pellegrinelli, Chicheportiche and Meier (2001) J. Clin. Endocrinol.

Immunomodulatory actions of leptin.

Leptin, the adipocyte-secreted hormone, exerts its main function as regulator of food intake and energy expenditure through central effects at the hypothalamic level. However, it appeared that this cytokine-like peptide has also direct effects on other peripheral tissues and cell types. Remarkable effects have been demonstrated on the immune function in vivo and in vitro.

Regulation of the interleukin-1 receptor antagonist in THP-1 cells by ligands of the peroxisome proliferator-activated receptor gamma.

Monocytes/macrophages (Mphi) play a pivotal role in the persistence of chronic inflammation and local tissue destruction in diseases such as rheumatoid arthritis and atherosclerosis. The production by Mphi of cytokines, chemokines, metalloproteinases and their inhibitors is an essential component in this process, which is tightly regulated by multiple factors. The peroxisome proliferator-activated receptors (PPARs) were shown to be involved in modulating inflammation.