Chemokines control fat accumulation and leptin secretion by cultured human adipocytes

• Published in: Molecular and cellular endocrinology 2001-04, Vol.175 (1), p.81-92
• Main Authors: Gerhardt, C.C., Romero, I.A., Cancello, R., Camoin, L., Strosberg, A.D.
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - chemistry; Adipocytes - drug effects; Adipocytes - metabolism; Cell Differentiation - drug effects; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokine CCL3; Chemokine CCL4; Chemokine receptors; Chemokines - genetics; Chemokines - metabolism; Chemokines - pharmacology; Humans; IL-8; Immunohistochemistry; Insulin; Interleukin-8 - genetics; Interleukin-8 - metabolism; Leptin; Leptin - metabolism; Macrophage Inflammatory Proteins - genetics; Macrophage Inflammatory Proteins - metabolism; MCP-1; MIP1α; Obesity; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Receptors, Leptin; RNA, Messenger - metabolism; Triglycerides - metabolism; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - pharmacology; Up-Regulation - drug effects
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(01)00394-X

In addition to their role in inflammation, cytokines like TNFα have been reported to regulate the adipose tissue function suggesting a role for these soluble mediators in metabolism. However, it is not known whether adipocytes have the capacity to secrete chemokines, a group of low molecular weight inflammatory mediators that control leukocyte migration into tissues. Here we show that primary cultures of human preadipocytes constitutively produce three chemokines, interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1), while their level of expression is low in mature adipocytes. Upon TNFα treatment, the expression of all the three chemokines is upregulated in adipocytes differentiated in vitro. In addition, we describe the presence of seven different chemokine receptors, mainly in mature adipocytes, both in vitro and in human fat tissue sections. Prolonged stimulation of cultured human adipocytes with exogenous chemokines leads to a decrease in lipid content in association with the downregulation of PPARγ mRNA expression. Moreover, chemokines positively control the secretion of leptin, a hormone that regulates appetite, by a post-transcriptional mechanism. These findings reveal a new role for chemokines in the regulation of adipose tissue and suggest a novel therapeutic basis for the treatment of obesity, diabetes and cachexia.