extract improves senescence-associated metabolic dysfunction by targeting inflammation in adipose tissue and macrophage in obesity-induced insulin resistance mice.

Insulin Resistance (IR) is a complication that frequently occurs in obesity. The inflammation-mediated senescence in White Adipose Tissue (WAT) is important in obesity-induced IR. Centella asiatica (CA) is a potential medicinal plant with anti-aging and anti-obesity properties. Here, we explored the effect of CA on obesity-mediated IR in mice fed with a High Fat-High Fructose (HFHF) diet and treated simultaneously with CA at 150 mg/kgBW (CA150) or 300 mg/kgBW (CA300). The total body mass and visceral WAT weight in both CA groups decreased in comparison with HFHF group alone. We demonstrated that HFHF-diet mice treated with CA300 improved insulin sensitivity and enhanced activation in WAT. CA300, but not CA150, prevented the senescence phenotype in WAT, represented by decreased Senescence-associated beta-galactosidase (SA-β-Gal) activity and diminished and expression levels at mRNA level. Mechanistically, CA300 prevented the enhancement of and mRNA expression levels and macrophage activity in the immunostaining analysis of WAT. , RAW264.7 cells stimulated with high glucose and low dose of Lipopolysaccharides (LPS) also confirmed that CA 200 μg/ml alleviated the expression levels of M1 markers such as , , , and at mRNA level. Our data indicated that CA has therapeutic potential for obesity-mediated IR by suppressing proinflammatory M1 macrophages and preventing inflammation-induced senescence in WAT.