SUMMARY
Background : Rosmarinic acid (RA) is a natural phenol carboxylic acid with many promising biological effects. It may be a suitable candidate for improving obesity-related adipose tissue dysfunction.Objective : We aimed to investigate the therapeutic use of RA as an anti-obesity agent by measuring its effects on adipogenesis, lipolysis, and messenger RNA (mRNA) expression of major adipokines in 3T3-L1 adipocytes; and its effects on lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-a) secretion in macrophages and inflammatory mediators in 3T3-L1 adipocytes incubated with macrophage-conditioned medium (MCM).Methods : 3T3-L1 preadipocytes were used to explore how RA affects adipogenesis, as well as the involvement of phosphorylated extracellular signal-regulated kinase-1/2 (p-ERK1/2) and mothers against decapentaplegic homolog 3 (p-Smad3). 3T3-L1 preadipocytes were also differentiated into mature adipocytes to explore how RA affects basal and isoproterenol- and forskolin-stimulated lipolysis; and how RA affects key adipokines’ mRNA expression. RAW 264.7 macrophages were stimulated with LPS in the absence or presence of RA to explore RA’s effects on TNF-a secretion. MCM was collected and 3T3-L1 adipocytes were incubated with MCM to explore RA’s effects on interleukin-6 (IL-6), IL-1ß, monocyte chemoattractant protein-1 (MCP-1), and RANTES mRNA expression.Results : During the preadipocyte differentiation process, RA suppressed peroxisome proliferator-activated receptor-? and CCAAT/enhancer binding protein-a, and activated p-ERK1/2 and p-Smad3; inhibition of adipogenesis by RA was partially restored following treatment with p-ERK1/2 and p-Smad3 inhibitors. In mature adipocytes, RA inhibited basal lipolysis; phosphodiesterase-3 inhibitor reversed this. RA also inhibited isoproterenol- and forskolin-stimulated glycerol and free fatty acid release, and the phosphorylation of hormone-sensitive lipase and perilipin. RA had no effects on leptin, adiponectin, resistin, or visfatin mRNA expression. RA suppressed TNF-a mRNA expression and secretion in LPS-stimulated RAW 264.7 macrophages; and reduced LPS-MCM-induced IL-6, IL-1ß, MCP-1, and RANTES mRNA expression in 3T3-L1 adipocytes.Conclusions : RA exerts inhibitory effects on adipogenesis, lipolysis, and inflammation. RA could be a promising natural product for improving adipose mobilization in obesity.