title: Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease: the protective effects of pomegranate with its active component punicalagin.
abstract: OBJECTIVE
  Punicalagin (PU) is one of the major ellagitannins found in the pomegranate (Punica granatum), which is a popular fruit with several health benefits. So far, no studies have evaluated the effects of PU on nonalcoholic fatty liver disease (NAFLD). Our work aims at studying the effect of PU-enriched pomegranate extract (PE) on high fat diet (HFD)-induced NAFLD.
  
  
  RESULTS
  PE administration at a dosage of 150 mg/kg/day significantly inhibited HFD-induced hyperlipidemia and hepatic lipid deposition. As major contributors to NAFLD, increased expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukins 1, 4, and 6 as well as augmented oxidative stress in hepatocytes followed by nuclear factor (erythroid-derived-2)-like 2 (Nrf2) activation were normalized through PE supplementation. In addition, PE treatment reduced uncoupling protein 2 (UCP2) expression, restored ATP content, suppressed mitochondrial protein oxidation, and improved mitochondrial complex activity in the liver. In contrast, mitochondrial content was not affected despite increased peroxisomal proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and elevated expression of genes related to mitochondrial beta-oxidation after PE treatment. Finally, PU was identified as the predominant active component of PE with regard to the lowering of triglyceride and cholesterol content in HepG2 cells, and both PU- and PE-protected cells from palmitate induced mitochondrial dysfunction and insulin resistance.
  
  
  METHODS
  Our work presents the beneficial effects of PE on obesity-associated NAFLD and multiple risk factors. PU was proposed to be the major active component.
  
  
  CONCLUSIONS
  By promoting mitochondrial function, eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of NAFLD.
authors.affiliation: 1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an, China .
authors.forename: Xuan
authors.initials: X
authors.lastname: Zou
authors.forename: Chunhong
authors.initials: C
authors.lastname: Yan
authors.forename: Yujie
authors.initials: Y
authors.lastname: Shi
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Wentao
authors.initials: W
authors.lastname: Pang
authors.forename: Jialong
authors.initials: J
authors.lastname: Zhao
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Adi
authors.initials: A
authors.lastname: Zheng
authors.forename: Wenyan
authors.initials: W
authors.lastname: Sun
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
authors.forename: Ignatius Man-Yau
authors.initials: IM
authors.lastname: Szeto
authors.forename: Youyou
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Peifang
authors.initials: P
authors.lastname: Zhang
authors.forename: Junkuan
authors.initials: J
authors.lastname: Wang
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C115642:punicalagin; D002784:Cholesterol