Antioxidant MMCC ameliorates catch-up growth related metabolic dysfunction

Liping Ju; Wenxin Tong; Miaoyan Qiu; Weili Shen; Jichao Sun; Sheng Zheng; Ying Chen; Wentao Liu; Jingyan Tian

doi:10.18632/oncotarget.21965

Antioxidant MMCC ameliorates catch-up growth related metabolic dysfunction

Oncotarget. 2017 Oct 23;8(59):99931-99939. doi: 10.18632/oncotarget.21965. eCollection 2017 Nov 21.

Authors

Liping Ju¹, Wenxin Tong^{1

2}, Miaoyan Qiu¹, Weili Shen³, Jichao Sun⁴, Sheng Zheng¹, Ying Chen¹, Wentao Liu⁵, Jingyan Tian^{1

2}

Affiliations

¹ Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, USA.
³ Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Laboratory of Endocrine and Metabolic Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Key Laboratory of Shanghai Gastric Neoplasms, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai Institute of Digestive Surgery, Shanghai, China.

Abstract

Postnatal catch-up growth may be related to reduce mitochondrial content and oxidation capacity in skeletal muscle. The aim of this study is to explore the effect and mechanism of antioxidant MitoQuinone mesylate beta cyclodextrin complex (MMCC) ameliorates catch-up growth related metabolic disorders. Catch-up growth mice were created by restricting maternal food intake during the last week of gestation and providing high fat diet after weaning. Low birthweight mice and normal birthweight controls were randomly subjected to normal fat diet, high fat diet and high fat diet with MMCC drinking from the 4th week. MMCC treatment for 21 weeks slowed down the catch up growth and ameliorated catch-up growth related obesity, glucose intolerance and insulin resistance. MMCC administration significantly inhibited the peroxidation of the membrane lipid and up-regulated the antioxidant enzymes Catalase and MnSOD. In addition, MMCC treatment effectively enhanced mitochondrial functions in skeletal muscle through the up-regulation of the ATP generation, and the promotion of mitochondrial replication and remodeling. To conclude, this study demonstrates that antioxidant MMCC effectively ameliorates catch-up growth related metabolic dysfunctions by increasing mitochondrial functions in skeletal muscle.

Keywords: MMCC (MitoQuinone mesylate beta cyclodextrin complex); catch-up growth; metabolic dysfunction; mitochondria; skeletal functions.