Targeting bile-acid signalling for metabolic diseases

被引：1138

作者：

Thomas, Charles ^{[1
]}

Pellicciari, Roberto ^{[2
]}

Pruzanski, Mark ^{[3
]}

Auwerx, Johan ^{[1
,4
,5
]}

Schoonjans, Kristina ^{[1
,5
]}

机构：

[1] Inst Genet & Mol & Cellular Biol, F-67404 Illkirch Graffenstaden, France

[2] Univ Perugia, Dept Chem & Pharmaceut Technol, I-06123 Perugia, Italy

[3] Intercept Pharmaceut, New York, NY 10013 USA

[4] Mouse Clin Inst, F-67404 Illkirch Graffenstaden, France

[5] Swiss Fed Inst Technol, CH-1015 Lausanne, Switzerland

来源：

NATURE REVIEWS DRUG DISCOVERY | 2008年 / 7卷 / 08期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nrd2619

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Bile acids are increasingly being appreciated as complex metabolic integrators and signalling factors and not just as lipid solubilizers and simple regulators of bile-acid homeostasis. It is therefore not surprising that a number of bile-acid-activated signalling pathways have become attractive therapeutic targets for metabolic disorders. Here, we review how the signalling functions of bile acids can be exploited in the development of drugs for obesity, type 2 diabetes, hypertriglyceridaemia and atherosclerosis, as well as other associated chronic diseases such as non-alcoholic steatohepatitis.

引用

页码：678 / 693

页数：16

共 161 条

[1]

ANGELIN B, 1978, J LIPID RES, V19, P1017

[2] Improving metabolism by increasing energy expenditure [J].

Auwerx, J .

NATURE MEDICINE, 2006, 12 (01) :44-45

[3] Transcriptional corepression by SHP:: molecular mechanisms and physiological consequences [J].

Båvner, A ;

Sanyal, S ;

Gustafsson, JÅ ;

Treuter, E .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2005, 16 (10) :478-488

[4] Human CYP7A1 deficiency:: Progress and enigmas [J].

Beigneux, A ;

Hofmann, AF ;

Young, SG .

JOURNAL OF CLINICAL INVESTIGATION, 2002, 110 (01) :29-31

[5] Activation of the farnesoid X receptor improves lipid metabolism in combined hyperlipidemic hamsters [J].

Bilz, S ;

Samuel, V ;

Morino, K ;

Savage, D ;

Choi, CS ;

Shulman, GI .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2006, 290 (04) :E716-E722

[6] THE METABOLISM OF CHENODEOXYCHOLIC ACID TO BETA-MURICHOLIC ACID IN RAT-LIVER [J].

BOTHAM, KM ;

BOYD, GS .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1983, 134 (01) :191-196

[7] The small heterodimer partner interacts with the liver X receptor α and represses its transcriptional activity [J].

Brendel, C ;

Schoonjans, K ;

Botrugno, OA ;

Treuter, E ;

Auwerx, J .

MOLECULAR ENDOCRINOLOGY, 2002, 16 (09) :2065-2076

[8] The farnesoid X receptor FXRα/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution [J].

Cai, Shi-Ying ;

Xiong, Liangshi ;

Wray, Charles G. ;

Ballatori, Nazzareno ;

Boyer, James L. .

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2007, 293 (03) :R1400-R1409

[9] Transient impairment of the adaptive response to fasting in FXR-deficient mice [J].

Cariou, B ;

van Harmelen, K ;

Duran-Sandoval, D ;

van Dijk, T ;

Grefhorst, A ;

Bouchaert, E ;

Fruchart, JC ;

Gonzalez, FJ ;

Kuipers, F ;

Staels, B .

FEBS LETTERS, 2005, 579 (19) :4076-4080

[10] The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice [J].

Cariou, B ;

van Harmelen, K ;

Duran-Sandoval, D ;

van Dijk, TH ;

Grefhorst, A ;

Abdelkarim, M ;

Caron, S ;

Torpier, G ;

Fruchart, JC ;

Gonzalez, FJ ;

Kuipers, F ;

Staels, B .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (16) :11039-11049

← 1 2 3 4 5 6 7 8 9 10 →