Ameliorating Oxidative Stress-Aggravated Adipose Tissue Senescence by Sesamol in Aged Obese Mice via Nrf2/p38MAPK Signaling.

Abstract

Adipocyte senescence is one of the major common features correlated with aging, which can also lead to obesity, and aggravated oxidative stress contributes to cell senescence. Sesamol, a lignan from plants found in sesame, has been proven to alleviate obesity. However, the effects and mechanisms of sesamol on adipose tissue senescence remain unclear. In the current research, we used an aged model of obesity by feeding old mice high-fat diet (HFD), and a senescent cell model by treating 3T3-L1 mature adipocytes with repeated exposure to hydrogen peroxide (H₂O₂). Both HFD induced aged obesity mice and H₂O₂ treated cells presented features associated with senescence. Additionally, obesity in aged mice accelerated the expression of adipose tissue senescence-associated markers. Notably, the presence of sesamol showed marked activation of Nrf2 and inhibition of p-p38MAPK, along with the suppression of oxidative stress (ROS, MDA, SOD), inflammatory factors (IL-6, TNFα) and cell cycle inhibitors (p53, p21, p16). A pretreatment of ML385, an inhibitor of Nrf2, reversed the effects induced by sesamol treatment. In conclusion, our results demonstrated that obesity contributed to deteriorated adipose tissue senescence during aging. Furthermore, sesamol, acted as an activator of Nrf2 and exerted negative impacts on the activation of p38MAPK, which were associated with amelioration of adipose senescence, thereby indicating it could be a potential nutritional intervention for preventing and treating aging-related disorders.