title: Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration.
abstract: OBJECTIVE
  Mitochondria and the endoplasmic reticulum (ER) physically interact by close structural juxtaposition, via the mitochondria-associated ER membrane. Inter-organelle communication between the ER and mitochondria has been shown to regulate energy metabolism and to be central to the modulation of various key processes such as ER stress. We aimed to clarify the role of mitochondrial fission in this communication.
  
  
  METHODS
  We generated mice lacking the mitochondrial fission protein dynamin-related protein 1 (DRP1) in the liver (Drp1LiKO mice).
  
  
  RESULTS
  Drp1LiKO mice showed decreased fat mass and were protected from high-fat diet (HFD)-induced obesity. Analysis of liver gene expression profiles demonstrated marked elevation of ER stress markers. In addition, we observed increased expression of the fibroblast growth factor 21 (FGF21) gene through induction of activating transcription factor 4, master regulator of the integrated stress response.
  
  
  CONCLUSIONS
  Disruption of mitochondrial fission in the liver provoked ER stress, while inducing the expression of FGF21 to increase energy expenditure and protect against HFD-induced obesity.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Ishihara
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ibayashi
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Tatsushima
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Setoyama
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hanada
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yukina
authors.initials: Y
authors.lastname: Takeichi
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Division of Functional Morphology, Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
authors.forename: Sadaki
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Mihara
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume, Japan.
authors.forename: Naotada
authors.initials: N
authors.lastname: Ishihara
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan. nomura@med.kyushu-u.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000818:Animals; D059305:Diet, High-Fat; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000235:genetics*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*
chemical_list: C414620:fibroblast growth factor 21; D051701:Activating Transcription Factor 4; D005346:Fibroblast Growth Factors; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: DRP1; ER stress; FGF 21; Mitochondrial dynamics; Mitochondria–ER juxtaposition structure