Legacy Effect of Antioxidant N-acetylcysteine in Cellular Senescence of Diet-induced Obesity Mice

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+NAC^1-12 (NAC intervention 1st-12th month), HFD+NAC^1-12, and HFD+NAC^1-6 (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+NAC^1-12 group exhibited increased MA, decreased BW and body fat, improved glucose tolerance, and decreased senescence markers.The HFD+NAC^1-6 group showed similar effects to the HFD+NAC^1-12 group, despite discontinuing NAC for 6 months. Our study showed that NAC significantly increased MA in both HFD+NAC^1-12 and HFD+NAC^1-6 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.

Cite this article as:

Tsao Cheng-Feng , Chang Yen-Hsiang, Shen Feng-Chih , Su Yu-Jih , Lin Hung-Yu , Chang Chia-Shiang , Lin Ching-Yi , Lian Wei-Shiung , Chuang Jiin-Haur , Lin Tsu-Kung , Liou Chia-Wei , Wang Pei-Wen and Weng Shao-Wen *, Legacy Effect of Antioxidant N-acetylcysteine in Cellular Senescence of Diet-induced Obesity Mice, Current Molecular Medicine 2021; 21 (6) . https://dx.doi.org/10.2174/1566524020999201113101738