Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration

被引：111

作者：

Wang, Lixiang ^{[1
]}

Ishihara, Takaya ^{[2
]}

Ibayashi, Yuta ^{[1
]}

Tatsushima, Keita ^{[1
]}

Setoyama, Daiki ^{[3
]}

Hanada, Yuki ^{[1
]}

Takeichi, Yukina ^{[1
]}

Sakamoto, Shohei ^{[1
]}

Yokota, Sadaki ^{[4
]}

Mihara, Katsuyoshi ^{[5
]}

Kang, Dongchon ^{[3
]}

Ishihara, Naotada ^{[2
]}

Takayanagi, Ryoichi ^{[1
]}

Nomura, Masatoshi ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan

[2] Kurume Univ, Dept Prot Biochem, Inst Life Sci, Kurume, Fukuoka 830, Japan

[3] Kyushu Univ, Dept Clin Chem & Lab Med, Grad Sch Med Sci, Fukuoka 8128582, Japan

[4] Nagasaki Int Univ, Fac Pharmaceut Sci, Div Funct Morphol, Sasebo, Nagasaki, Japan

[5] Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 8128582, Japan

来源：

DIABETOLOGIA | 2015年 / 58卷 / 10期

关键词：

DRP1; ER stress; FGF; 21; Mitochondria-ER juxtaposition structure; Mitochondrial dynamics; GROWTH-FACTOR; 21; ENDOPLASMIC-RETICULUM STRESS; INSULIN-RESISTANCE; ISLET HYPERPLASIA; FGF21; CELLS; INDUCTION; DYNAMICS; FUSION; LEADS;

D O I：

10.1007/s00125-015-3704-7

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aim/hypothesis 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/interpretation 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.

引用

页码：2371 / 2380

页数：10

共 35 条

[1] FGF21 Requires βklotho to Act In Vivo [J].

Adams, Andrew C. ;

Cheng, Christine C. ;

Coskun, Tamer ;

Kharitonenkov, Alexei .

PLOS ONE, 2012, 7 (11)

[2] Mitochondrial Dynamics - Mitochondrial Fission and Fusion in Human Diseases [J].

Archer, Stephen L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (23) :2236-2251

[3] Endoplasmic reticulum of animal cells and its organization into structural and functional domains [J].

Baumann, O ;

Walz, B .

INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 205, 2001, 205 :149-214

[4] Unfolded protein response [J].

Cao, Stewart Siyan ;

Kaufman, Randal J. .

CURRENT BIOLOGY, 2012, 22 (16) :R622-R626

[5] The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells [J].

Carracedo, A ;

Lorente, M ;

Egia, A ;

Blázquez, C ;

García, S ;

Giroux, V ;

Malicet, C ;

Villuendas, R ;

Gironella, M ;

González-Feria, L ;

Piris, MA ;

Iovanna, JL ;

Guzmán, M ;

Velasco, G .

CANCER CELL, 2006, 9 (04) :301-312

[6] Mitochondrial dynamics in cell life and death [J].

D Chan ;

S Frank ;

M Rojo .

Cell Death & Differentiation, 2006, 13 (4) :680-684

[7] Fibroblast Growth Factor 21 Corrects Obesity in Mice [J].

Coskun, Tamer ;

Bina, Holly A. ;

Schneider, Michael A. ;

Dunbar, James D. ;

Hu, Charlie C. ;

Chen, Yanyun ;

Moller, David E. ;

Kharitonenkov, Alexei .

ENDOCRINOLOGY, 2008, 149 (12) :6018-6027

[8] FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis [J].

Fisher, Ffolliott M. ;

Kleiner, Sandra ;

Douris, Nicholas ;

Fox, Elliott C. ;

Mepani, Rina J. ;

Verdeguer, Francisco ;

Wu, Jun ;

Kharitonenkov, Alexei ;

Flier, Jeffrey S. ;

Maratos-Flier, Eleftheria ;

Spiegelman, Bruce M. .

GENES & DEVELOPMENT, 2012, 26 (03) :271-281

[9] Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State [J].

Fisher, Ffolliott M. ;

Chui, Patricia C. ;

Antonellis, Patrick J. ;

Bina, Holly A. ;

Kharitonenkov, Alexei ;

Flier, Jeffrey S. ;

Maratos-Flier, Eleftheria .

DIABETES, 2010, 59 (11) :2781-2789

[10]

FOLCH J, 1957, J BIOL CHEM, V226, P497

← 1 2 3 4 →