Rosmarinic acid suppresses adipogenesis, lipolysis in 3T3-L1 adipocytes, lipopolysaccharide-stimulated tumor necrosis factor-α secretion in macrophages, and inflammatory mediators in 3T3-L1 adipocytes

Abstract

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-α (TNF-α) 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-α secretion. MCM was collected and 3T3-L1 adipocytes were incubated with MCM to explore RA’s effects on interleukin-6 (IL-6), IL-1β, monocyte chemoattractant protein-1 (MCP-1), and RANTES mRNA expression.Results: During the preadipocyte differentiation process, RA suppressed peroxisome proliferator-activated receptor-γ and CCAAT/enhancer binding protein-α, 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-α mRNA expression and secretion in LPS-stimulated RAW 264.7 macrophages; and reduced LPS-MCM-induced IL-6, IL-1β, 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.

The inhibitory effects of rosmarinic acid on catabolism induced by IL-1β in rat chondrocyte

“…In the present study, we treated the chondrocytes with IL-1β, as expected, the expression of ADAMTS-4 and ADAMTS-5 was increased after incubation with IL-1β, and the production of IL-6, an inflammatory cytokine, was also upregulated by IL-1β. RosA is known to exhibit anti-inflammatory activities, Rui and others (Rui et al, 2017) reported that RosA inhibited the expression of IL-6 in 3T3-L1 adipocytes. Our results showed that RosA can inhibit the secretion of IL-6.Therefore, the protective effects of RosA on chondrocytes may be partly associated with its antiinflammatory properties.…”

Effects of Fermented Houttuynia cordata Thunb. on Diabetic Rats Induced by a High-Fat Diet with Streptozotocin and on Insulin Resistance in 3T3-L1 Adipocytes

“…Likewise, the present study also demonstrated the presence of high levels of gallic acid and rosmarinic acid in fermented HC. Many studies showed that quercetin [54,55], rosmarinic acid [56], chlorogenic acid [57], rutin [58], and gallic acid [59] exhibited potential antioxidant, anti-inflammatory, and antidiabetic properties.…”

Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation

“…The results reflect what already happened in adipose tissue; there was a high level of glycerol and FFAs with a reduction of triglyceride levels in the blood of experimental rats that have been received FSK alone or with mevastatin during the experimental period ( Table 4 ). It has been approved that FSK stimulates glycerol and free fatty acids release from animal adipocytes [ 35 ], human adipose tissue [ 36 ], adipocytes cell lines [ 37 , 38 ], and mice adipose tissue [ 39 ]. Recently, FSK has been used as a new supplement for controlling obesity [ 40 ] while it has been found that FSK can decrease total body lipids percentage; this comes with an improvement for lean body mass [ 41 ]; this comes in the same line of our results.…”