Saroglitazar reduces obesity and associated inflammatory consequences in murine adipose tissue

• Published in: European journal of pharmacology 2018-03, Vol.822, p.32-42
• Main Authors: Kumar, Durgesh, Goand, Umesh Kumar, Gupta, Sanchita, Shankar, Kripa, Varshney, Salil, Rajan, Sujith, Srivastava, Ankita, Gupta, Abhishek, Vishwakarma, Achchhe Lal, Srivastava, Anurag Kumar, Gaikwad, Anil N.
• Format: Article
• Language: English
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Energy expenditure; Energy Metabolism - drug effects; Extracellular remodeling; Glucose - metabolism; Homeostasis - drug effects; Hypertrophy - drug therapy; Inflammation; Inflammation - metabolism; Inflammation - pathology; Insulin resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Obesity - drug therapy; Obesity - metabolism; Obesity - pathology; Organ Specificity; Phenylpropionates - pharmacology; Phenylpropionates - therapeutic use; PPARs; Pyrroles - pharmacology; Pyrroles - therapeutic use
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2018.01.002

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.