title: Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation.
abstract: Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders.
authors.affiliation: Center for Mitochondrial Biology and Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
authors.affiliation: Center for Mitochondrial Biology and Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Center for Mitochondrial Biology and Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Pu
authors.affiliation: Nestlé Research Center Beijing, Beijing, 100095, China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Weijin
authors.initials: W
authors.lastname: Zang
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Center for Mitochondrial Biology and Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport, Tianjin, 300381, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Mitochondrial Biology and Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Center for Mitochondrial Biology and Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport, Tianjin, 300381, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D029561:Lythraceae / Q000737:chemistry*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D001678:Organelle Biogenesis; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047348:Hydrolyzable Tannins; C115642:punicalagin; D055372:AMP-Activated Protein Kinases