Title:Legacy Effect of Antioxidant N-acetylcysteine in Cellular Senescence of Diet-induced Obesity Mice
Volume: 21
Issue: 6
Author(s): Cheng-Feng Tsao, Yen-Hsiang Chang, Feng-Chih Shen, Yu-Jih Su, Hung-Yu Lin, Chia-Shiang Chang, Ching-Yi Lin, Wei-Shiung Lian, Jiin-Haur Chuang, Tsu-Kung Lin, Chia-Wei Liou, Pei-Wen Wang and Shao-Wen Weng*
Affiliation:
- Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833,Taiwan
Keywords:
Cellular senescence, obesity, insulin resistance, type 2 diabetes, legacy effect, N-acetylcysteine.
Abstract:
Background: Cellular senescence is a state of stable growth arrest triggered
by mitogenic and metabolic stressors. Ageing and a high-fat diet (HFD) are proven
inducers of senescence in various organs, presenting a challenge for ageing populations
worldwide. Our previous study demonstrated that ROS scavenger N-acetylcysteine
(NAC) can improve insulin resistance (IR) and chronic inflammation in diet-induced
obesity mice, an effect better achieved through early intervention. We, herein,
investigate whether NAC can improve cellular senescence in a diet-induced obesity
mouse model, and whether a legacy effect is presented with early intervention.
Materials and Methods: For a twelve-month treatment course, all C57B/L6 mice were
fed a chow diet (CD), high-fat high-sucrose diet (HFD), CD+NAC1-12 (NAC intervention
1st-12th month), HFD+NAC1-12, and HFD+NAC1-6 (NAC intervention 1st-6th month).
Staticalanalysis was used to analyze the different markers of cellular senescence and
inflammation.
Results: Throughout the study, the HFD group exhibited significantly increased body
weight (BW) and body fat, markers of senescence, decreased motor activity (MA) and
impaired glucose tolerance. Compared to the HFD group, the HFD+NAC1-12 group
exhibited increased MA, decreased BW and body fat, improved glucose tolerance, and
decreased senescence markers.The HFD+NAC1-6 group showed similar effects to the
HFD+NAC1-12 group, despite discontinuing NAC for 6 months. Our study showed that NAC
significantly increased MA in both HFD+NAC1-12 and HFD+NAC1-6 groups, and improved
HFD-induced mitochondrial and intracellular ROS expression, DNA and protein oxidative
damage, and adipose tissue inflammation.
Conclusion: Legacy effect was indeed presented in HFD-induced cellular senescence
with NAC intervention, with possible mechanisms being persistently increased motor
activity and anti-oxidative stress effects.
