title: Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.
abstract: Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32 mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.
authors.affiliation: 1] Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan [2] Central Laboratory, Pokka Sapporo Food & Beverage Ltd., Aichi, Japan [3].
authors.forename: Masanori
authors.initials: M
authors.lastname: Hiramitsu
authors.affiliation: 1] Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan [2] Mie University Medical Zebrafish Research Center, Mie, Japan [3] Department of Systems Pharmacology, Mie University Graduate School of Medicine, Mie, Japan [4] Department of Bioinformatics, Mie University Life Science Research Center, Mie, Japan [5] Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Mie, Japan [6].
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroyanagi
authors.affiliation: Central Laboratory, Pokka Sapporo Food & Beverage Ltd., Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Central Laboratory, Pokka Sapporo Food & Beverage Ltd., Aichi, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Katagiri
authors.affiliation: Department of Translational Medical Science, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zang
authors.affiliation: 1] Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan [2] Mie University Medical Zebrafish Research Center, Mie, Japan [3] Department of Systems Pharmacology, Mie University Graduate School of Medicine, Mie, Japan [4] Department of Bioinformatics, Mie University Life Science Research Center, Mie, Japan [5] Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Mie, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Translational Medical Science, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimura
authors.affiliation: 1] Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan [2] Mie University Medical Zebrafish Research Center, Mie, Japan [3] Department of Systems Pharmacology, Mie University Graduate School of Medicine, Mie, Japan [4] Department of Bioinformatics, Mie University Life Science Research Center, Mie, Japan [5] Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Mie, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002957:Citrus / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids / Q000502:physiology; D008099:Liver / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D001678:Organelle Biogenesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015027:Zebrafish
chemical_list: D004272:DNA, Mitochondrial; D044950:Flavanones; D005419:Flavonoids; D008055:Lipids; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; C114706:eriocitrin