In addition to their role in inflammation, cytokines like TNFalpha 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-1alpha (MIP-1alpha) and monocyte chemotactic protein-1 (MCP-1), while their
level of expression is low in mature adipocytes. Upon TNFalpha 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 PPARgamma 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.