| Status | 已發表Published |
| Identification of therapeutic agents for treatment of metabolic diseases targeting adipose tissue inflammation | |
Li, D. ; Liu, J.; Ye, Y.; Lin, L. 
| |
| 2017-10-01 | |
| Source Publication | The 4th Eskitis-SIMM International Symposium
 |
| Abstract | Chronic inflammation in adipose tissue plays a critical role in the onset and development of metabolic disorders, such as insulin resistance and type 2 diabetes. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. Here, we show that in aged mice, the ghrelin receptor, growth hormone secretagogue receptor (GHS-R) ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsr-/- mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white adipose tissues. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Old Ghsr-/- mice exhibit a lean and insulin-sensitive phonotype. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. The fruit hull of Garcinia mangostana has been used in traditional medicine for treatment of various inflammatory diseases. In current study, 1,3,6,7-tetrahydroxy-8-prenylxanthone (TPX) was identified as the most potent active molecule on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and interleukin-6 (IL-6) secretion in RAW264.7 macrophages, among a series of xanthones from G. mangostana. TPX ameliorated LPS-induced inflammatory responses in RAW264.7 macrophages, and tumor necrosis factor α (TNF-α) mediated inflammation in 3T3-L1 adipocytes, through inhibiting the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) activation, and promoting sirtuin3 (SIRT3) and peroxisome proliferator-activated receptors (PPARs) levels. In addition, TPX blocked RAW264.7 macrophages migration to 3T3-L1 adipocyte in co-culture system. In vivo, TPX alleviated LPS-induced adipose tissue inflammation in mice by reducing pro-inflammatory cytokines and promoting macrophage phenotypical shift from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages in abdominal adipose tissue. Overall, the above results demonstrated that TPX might represent a novel therapeutic agent for treatment of adipose tissue inflammation and related metabolic disorders. |
| Keyword | Garcinia mangostana adipose tissue inflammation macrophage |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 36316 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Lin, L. |
| Recommended Citation GB/T 7714 | Li, D.,Liu, J.,Ye, Y.,et al. Identification of therapeutic agents for treatment of metabolic diseases targeting adipose tissue inflammation[C], 2017. |
| APA | Li, D.., Liu, J.., Ye, Y.., & Lin, L. (2017). Identification of therapeutic agents for treatment of metabolic diseases targeting adipose tissue inflammation. The 4th Eskitis-SIMM International Symposium. |
| Files in This Item: | There are no files associated with this item. | |||||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment