title: Effect of metabolic syndrome on mitsugumin 53 expression and function.
abstract: Metabolic syndrome is a cluster of risk factors, such as obesity, insulin resistance, and hyperlipidemia that increases the individual's likelihood of developing cardiovascular diseases. Patients inflicted with metabolic disorders also suffer from tissue repair defect. Mitsugumin 53 (MG53) is a protein essential to cellular membrane repair. It facilitates the nucleation of intracellular vesicles to sites of membrane disruption to create repair patches, contributing to the regenerative capacity of skeletal and cardiac muscle tissues upon injury. Since individuals suffering from metabolic syndrome possess tissue regeneration deficiency and MG53 plays a crucial role in restoring membrane integrity, we studied MG53 activity in mice models exhibiting metabolic disorders induced by a 6 month high-fat diet (HFD) feeding. Western blotting showed that MG53 expression is not altered within the skeletal and cardiac muscles of mice with metabolic syndrome. Rather, we found that MG53 levels in blood circulation were actually reduced. This data directly contradicts findings presented by Song et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494, 375-379). The diminished MG53 serum level observed may contribute to the inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore, immunohistochemical analyses reveal that skeletal muscle fibers of mice with metabolic disorders experience localization of subcellular MG53 around mitochondria. This clustering may represent an adaptive response to oxidative stress resulting from HFD feeding and may implicate MG53 as a guardian to protect damaged mitochondria. Therapeutic approaches that elevate MG53 expression in serum circulation may be a novel method to treat the degenerative tissue repair function of diabetic patients.
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America; Olentangy Liberty High School, Powell, Ohio, United States of America.
authors.forename: Hanley
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America; Dublin Jerome High School, Dublin, Ohio, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: T M Ayodele
authors.initials: TM
authors.lastname: Adesanya
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Frank
authors.initials: F
authors.lastname: Yi
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Zhishui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000097:blood* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D008565:Membrane Proteins; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D002352:Carrier Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins