PMID- 28659738 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1654-661X (Print) IS - 1654-661X (Electronic) IS - 1654-661X (Linking) VI - 61 IP - 1 DP - 2017 TI - Rosmarinic acid suppresses adipogenesis, lipolysis in 3T3-L1 adipocytes, lipopolysaccharide-stimulated tumor necrosis factor-alpha secretion in macrophages, and inflammatory mediators in 3T3-L1 adipocytes. PG - 1330096 LID - 10.1080/16546628.2017.1330096 [doi] LID - 1330096 AB - 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-alpha (TNF-alpha) 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-alpha secretion. MCM was collected and 3T3-L1 adipocytes were incubated with MCM to explore RA's effects on interleukin-6 (IL-6), IL-1beta, monocyte chemoattractant protein-1 (MCP-1), and RANTES mRNA expression. Results: During the preadipocyte differentiation process, RA suppressed peroxisome proliferator-activated receptor-gamma and CCAAT/enhancer binding protein-alpha, 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-alpha mRNA expression and secretion in LPS-stimulated RAW 264.7 macrophages; and reduced LPS-MCM-induced IL-6, IL-1beta, 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. FAU - Rui, Yehua AU - Rui Y AD - Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China. FAU - Tong, Lingxia AU - Tong L AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, PR China. FAU - Cheng, Jinbo AU - Cheng J AD - Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China. FAU - Wang, Guiping AU - Wang G AD - Laboratory Animal Center, Soochow University, Suzhou, PR China. FAU - Qin, Liqiang AU - Qin L AD - Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China. FAU - Wan, Zhongxiao AU - Wan Z AD - Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, PR China. AD - Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, Soochow University, Suzhou, PR China. LA - eng PT - Journal Article DEP - 20170607 PL - Sweden TA - Food Nutr Res JT - Food & nutrition research JID - 101488795 PMC - PMC5475298 OTO - NOTNLM OT - Rosmarinic acid OT - adipocytes OT - adipogenesis OT - adipokines OT - lipolysis EDAT- 2017/07/01 06:00 MHDA- 2017/07/01 06:01 PMCR- 2017/06/07 CRDT- 2017/06/30 06:00 PHST- 2016/12/21 00:00 [received] PHST- 2017/05/05 00:00 [accepted] PHST- 2017/06/30 06:00 [entrez] PHST- 2017/07/01 06:00 [pubmed] PHST- 2017/07/01 06:01 [medline] PHST- 2017/06/07 00:00 [pmc-release] AID - 1330096 [pii] AID - 10.1080/16546628.2017.1330096 [doi] PST - epublish SO - Food Nutr Res. 2017 Jun 7;61(1):1330096. doi: 10.1080/16546628.2017.1330096. eCollection 2017.