TY - JOUR
T1 - Saroglitazar reduces obesity and associated inflammatory consequences in murine adipose tissue
AU - Kumar, Durgesh
AU - Goand, Umesh Kumar
AU - Gupta, Sanchita
AU - Shankar, Kripa
AU - Varshney, Salil
AU - Rajan, Sujith
AU - Srivastava, Ankita
AU - Gupta, Abhishek
AU - Vishwakarma, Achchhe Lal
AU - Srivastava, Anurag Kumar
AU - Gaikwad, Anil N.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/3/5
Y1 - 2018/3/5
N2 - 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.
AB - 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.
KW - Energy expenditure
KW - Extracellular remodeling
KW - Inflammation
KW - Insulin resistance
KW - Obesity
KW - PPARs
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U2 - 10.1016/j.ejphar.2018.01.002
DO - 10.1016/j.ejphar.2018.01.002
M3 - Article
C2 - 29331565
AN - SCOPUS:85041614174
SN - 0014-2999
VL - 822
SP - 32
EP - 42
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -