Introduction: Immunosuppressant agents modulate the activity of the immune system and
control adipose tissue inflammatory responses associated with obesity. Controlling adipose tissue
inflammation represents an interesting option for inhibiting the low-grade inflammatory state in
obese subjects and for preventing obesity-associated pathologies. In this work, we assessed the
effects of thalidomide on the inflammatory response in adipose tissue as well as on systemic
inflammatory marker expression in the well-established high-fat diet-induced obesity mouse model.
Methods: Swiss male mice were fed a high-fat diet (60% kcal from fat) for 12 weeks and received
thalidomide for the last 10 days (100 mg.kg-1). Adipokine levels were measured in serum and adipose tissue by EIA and
real-time quantitative PCR, respectively. Adipose tissue infiltrating macrophages were identified by immunohistochemistry
and western blot analysis of F4/80 marker expression. Other inflammatory markers, such as c-Jun N-terminal kinase (JNK)
phosphorylation and monocyte chemoattractant protein-1 (MCP-1) production, were also evaluated by western blot
analysis. In vitro assays using 3T3-L1 adipocytes were also conducted to evaluated adipokine release.
Results: In obese mice, thalidomide administration induced a reduction in adiposity accompanied by a reduction of tumor
necrosis factor-α (TNF-α), leptin and MCP-1 adipose tissue production, macrophage infiltration and JNK activation.
TNF-α and leptin serum levels were also reduced by thalidomide treatment in obese mice. In vitro, the release of basal
TNF-α and lipopolysaccharide (LPS)-induced MCP-1 was inhibited in 3T3-L1 cells.
Significance: Our results suggest that drugs that can modulate the inflammatory status as well as control adipose tissue
expansion could represent an interesting approach in the management of obesity, highlighting the need for further
development of such compounds.