Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, CSIR-CDRI, India.
Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India; National Institute of Pharmaceutical Education and Research, Raebareli 229010, India.
Eur J Pharmacol. 2018 Mar 5;822:32-42. doi: 10.1016/j.ejphar.2018.01.002. Epub 2018 Jan 10.
Prevailing knowledge links chronic low-grade inflammation in the adipose tissue to obesity and its associated metabolic complications. In this study, we evaluated immunometabolic effects of a recently launched dual peroxisome proliferator-activated receptor (PPAR) α & γ agonist 'Saroglitazar' in a mouse model of diet-induced obesity (DIO). Body composition analysis revealed that saroglitazar treatment promoted hepatic weight gain, while attenuated epididymal white adipose tissue (eWAT) mass in DIO. In the eWAT of saroglitazar treated mice, histological analysis showed reduced adipocyte hypertrophy and matrix deposition (picrosirius red staining). Immunological profiling of stromal vascular fraction isolated from eWAT showed decreased pro-inflammatory cells (M1 macrophages, CD4 and CD8 T-cells) and increased anti-inflammatory M2 macrophages. Gene expression and western blot analysis suggested that saroglitazar promoted energy expenditure machinery and attenuated inflammatory as well as fibrotic markers in eWAT during DIO. In conclusion, for the first time we are reporting immunometabolic effects of dual PPARα & γ agonist saroglitazar in DIO and insulin resistance (IR). Saroglitazar exerted its beneficial effects on adipose tissue by limiting, diet-induced adipose tissue dysfunction, adipocyte hypertrophy, adipocyte cell damage and extracellular matrix deposition in obesity.
目前的知识将脂肪组织中的慢性低度炎症与肥胖及其相关的代谢并发症联系起来。在这项研究中，我们评估了最近推出的双重过氧化物酶体增殖物激活受体（PPAR）α和γ激动剂“沙格列汀”在饮食诱导肥胖（DIO）小鼠模型中的免疫代谢作用。身体成分分析显示，沙格列汀治疗促进了肝脏重量的增加，同时减轻了附睾白色脂肪组织（eWAT）的质量。在沙格列汀治疗的小鼠的 eWAT 中，组织学分析显示脂肪细胞肥大和基质沉积减少（苦味酸天狼星红染色）。从 eWAT 分离的基质血管部分的免疫分析显示促炎细胞（M1 巨噬细胞、CD4 和 CD8 T 细胞）减少，抗炎 M2 巨噬细胞增加。基因表达和 Western blot 分析表明，沙格列汀在 DIO 和胰岛素抵抗（IR）期间促进了能量消耗机制，并减弱了 eWAT 中的炎症和纤维化标志物。总之，我们首次报道了双重 PPARα和γ激动剂沙格列汀在 DIO 和胰岛素抵抗中的免疫代谢作用。沙格列汀通过限制饮食诱导的脂肪组织功能障碍、脂肪细胞肥大、脂肪细胞损伤和细胞外基质沉积，对肥胖中的脂肪组织发挥了有益作用。
