Fat Mass and Obesity Associated (FTO) Gene and Hepatic Glucose and Lipid Metabolism

被引：110

作者：

Mizuno, Tooru M. ^{[1
]}

机构：

[1] Univ Manitoba, Div Endocrinol & Metab Dis, Dept Physiol & Pathophysiol, Max Rady Coll Med,Rady Fac Hlth Sci, Winnipeg, MB R3E 0J9, Canada

来源：

NUTRIENTS | 2018年 / 10卷 / 11期

关键词：

FTO; liver; gluconeogenesis; lipogenesis; glucose; insulin; type; 2; diabetes; non-alcoholic fatty liver disease; DEFICIENCY PROTECTS; OXIDATIVE STRESS; ATF4; PROTEIN; EXPRESSION; RNA; TRANSCRIPTION; SEQUENCE; INSULIN; MICE; N6-METHYLADENOSINE;

D O I：

10.3390/nu10111600

中图分类号：

R15 [营养卫生、食品卫生]; TS201 [基础科学];

学科分类号：

100403 ;

摘要：

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed. Earlier studies have focused on the role of hypothalamic FTO in the regulation of metabolism. However, recent studies suggest that expression of hepatic FTO is regulated by metabolic signals, such as nutrients and hormones, and altered FTO levels in the liver affect glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

引用

页数：11

共 63 条

[1] Loss-of-Function Mutation in the Dioxygenase-Encoding FTO Gene Causes Severe Growth Retardation and Multiple Malformations [J].

Boissel, Sarah ;

Reish, Orit ;

Proulx, Karine ;

Kawagoe-Takaki, Hiroko ;

Sedgwick, Barbara ;

Yeo, Giles S. H. ;

Meyre, David ;

Golzio, Christelle ;

Molinari, Florence ;

Kadhom, Noman ;

Etchevers, Heather C. ;

Saudek, Vladimir ;

Farooqi, I. Sadaf ;

Froguel, Philippe ;

Lindahl, Tomas ;

O'Rahilly, Stephen ;

Munnich, Arnold ;

Colleaux, Laurence .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (01) :106-111

[2] FTO contributes to hepatic metabolism regulation through regulation of leptin action and STAT3 signalling in liver [J].

Bravard, Amelie ;

Vial, Guillaume ;

Chauvin, Marie-Agnes ;

Rouille, Yves ;

Bailleul, Bernard ;

Vidal, Hubert ;

Rieusset, Jennifer .

CELL COMMUNICATION AND SIGNALING, 2014, 12

[3] Early Hypothalamic FTO Overexpression in Response to Maternal Obesity - Potential Contribution to Postweaning Hyperphagia [J].

Caruso, Vanni ;

Chen, Hui ;

Morris, Margaret J. .

PLOS ONE, 2011, 6 (09)

[4] Development of Cell-Active N6-Methyladenosine RNA Demethylase FTO Inhibitor [J].

Chen, Baoen ;

Ye, Fei ;

Yu, Lu ;

Jia, Guifang ;

Huang, Xiaotian ;

Zhang, Xueju ;

Peng, Shuying ;

Chen, Kai ;

Wang, Meining ;

Gong, Shouze ;

Zhang, Ruihan ;

Yin, Jinya ;

Li, Haiyan ;

Yang, Yiming ;

Liu, Hong ;

Zhang, Jiwen ;

Zhang, Haiyan ;

Zhang, Ao ;

Jiang, Hualiang ;

Luo, Cheng ;

Yang, Cai-Guang .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2012, 134 (43) :17963-17971

[5] FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice [J].

Chen, Jingqing ;

Zhou, Xihong ;

Wu, Weiche ;

Wang, Xinxia ;

Wang, Yizhen .

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, 2015, 71 (03) :405-413

[6] Overexpression of Fto leads to increased food intake and results in obesity [J].

Church, Chris ;

Moir, Lee ;

McMurray, Fiona ;

Girard, Christophe ;

Banks, Gareth T. ;

Teboul, Lydia ;

Wells, Sara ;

Bruening, Jens C. ;

Nolan, Patrick M. ;

Ashcroft, Frances M. ;

Cox, Roger D. .

NATURE GENETICS, 2010, 42 (12) :1086-U147

[7] A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene [J].

Church, Chris ;

Lee, Sheena ;

Bagg, Eleanor A. L. ;

McTaggart, James S. ;

Deacon, Robert ;

Gerken, Thomas ;

Lee, Angela ;

Moir, Lee ;

Mecinovic, Jasmin ;

Quwailid, Mohamed M. ;

Schofield, Christopher J. ;

Ashcroft, Frances M. ;

Cox, Roger D. .

PLOS GENETICS, 2009, 5 (08)

[8] Variation in FTO contributes to childhood obesity and severe adult obesity [J].

Dina, Christian ;

Meyre, David ;

Gallina, Sophie ;

Durand, Emmanuelle ;

Koerner, Antje ;

Jacobson, Peter ;

Carlsson, Lena M. S. ;

Kiess, Wieland ;

Vatin, Vincent ;

Lecoeur, Cecile ;

Delplanque, Jerome ;

Vaillant, Emmanuel ;

Pattou, Francois ;

Ruiz, Juan ;

Weill, Jacques ;

Levy-Marchal, Claire ;

Horber, Fritz ;

Potoczna, Natascha ;

Hercberg, Serge ;

Le Stunff, Catherine ;

Bougneres, Pierre ;

Kovacs, Peter ;

Marre, Michel ;

Balkau, Beverley ;

Cauchi, Stephane ;

Chevre, Jean-Claude ;

Froguel, Philippe .

NATURE GENETICS, 2007, 39 (06) :724-726

[9] Inactivation of the Fto gene protects from obesity [J].

Fischer, Julia ;

Koch, Linda ;

Emmerling, Christian ;

Vierkotten, Jeanette ;

Peters, Thomas ;

Bruening, Jens C. ;

Ruether, Ulrich .

NATURE, 2009, 458 (7240) :894-U10

[10] A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity [J].

Frayling, Timothy M. ;

Timpson, Nicholas J. ;

Weedon, Michael N. ;

Zeggini, Eleftheria ;

Freathy, Rachel M. ;

Lindgren, Cecilia M. ;

Perry, John R. B. ;

Elliott, Katherine S. ;

Lango, Hana ;

Rayner, Nigel W. ;

Shields, Beverley ;

Harries, Lorna W. ;

Barrett, Jeffrey C. ;

Ellard, Sian ;

Groves, Christopher J. ;

Knight, Bridget ;

Patch, Ann-Marie ;

Ness, Andrew R. ;

Ebrahim, Shah ;

Lawlor, Debbie A. ;

Ring, Susan M. ;

Ben-Shlomo, Yoav ;

Jarvelin, Marjo-Riitta ;

Sovio, Ulla ;

Bennett, Amanda J. ;

Melzer, David ;

Ferrucci, Luigi ;

Loos, Ruth J. F. ;

Barroso, Ines ;

Wareham, Nicholas J. ;

Karpe, Fredrik ;

Owen, Katharine R. ;

Cardon, Lon R. ;

Walker, Mark ;

Hitman, Graham A. ;

Palmer, Colin N. A. ;

Doney, Alex S. F. ;

Morris, Andrew D. ;

Smith, George Davey ;

Hattersley, Andrew T. ;

McCarthy, Mark I. .

SCIENCE, 2007, 316 (5826) :889-894

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