G-protein-coupled receptors for free fatty acids: nutritional and therapeutic targets

British Journal of Nutrition - Tập 111 Số S1 - Trang S3-S7 - 2014
Graeme Milligan1, Trond Ulven2, Hannah Murdoch1, Brian D. Hudson1
1Molecular Pharmacology Group, College of Medical, Veterinary and Life Sciences, Institute of Molecular, Cell and Systems Biology, University of Glasgow, Wolfson Link Building 253, University Avenue, GlasgowG12 8QQ, UK
2Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230Odense M, Denmark

Tóm tắt

It is becoming evident that nutrients and metabolic intermediates derived from such nutrients regulate cellular function by activating a number of cell-surface G-protein coupled receptors (GPCRs). Until now, members of the GPCR family have largely been considered as the molecular targets that communicate cellular signals initiated by hormones and neurotransmitters. Recently, based on tissue expression patterns of these receptors and the concept that they may elicit the production of a range of appetite- and hunger-regulating peptides, such nutrient sensing GPCRs are attracting considerable attention due to their potential to modulate satiety, improve glucose homeostasis and supress the production of various pro-inflammatory mediators. Despite the developing interests in these nutrients sensing GPCR both as sensors of nutritional status, and targets for limiting the development of metabolic diseases, major challenges remain to exploit their potential for therapeutic purposes. Mostly, this is due to limited characterisation and validation of these receptors because of paucity of selective and high-potency/affinity pharmacological agents to define the detailed function and regulation of these receptors. However, ongoing clinical trials of agonists of free fatty acid receptor 1 suggest that this receptor and other receptors for free fatty acids may provide a successful strategy for controlling hyperglycaemia and providing novel approaches to treat diabetes. Receptors responsive to free fatty acid have been of particular interest, and some aspects of these are considered herein.

Từ khóa


Tài liệu tham khảo

10.1016/j.cell.2010.08.022

10.1038/clpt.2012.43

10.3168/jds.2011-4886

10.1007/s00125-008-1202-x

10.1016/S0140-6736(11)61879-5

10.1371/journal.pone.0042373

Hoveyda, 2010, Compounds, pharmaceutical composition and methods for use in treating metabolic disorders, International patent application WO 2010/066682 A1

10.1053/j.gastro.2010.10.012

10.2337/db11-1019

10.1111/j.1365-2125.2012.04374.x

10.1124/pr.108.00802

10.1096/fj.12-213314

10.1074/jbc.M112.396259

10.1016/S0140-6736(12)60165-2

10.1074/jbc.M110.210872

10.1074/jbc.M109.012849

10.1124/mol.112.079640

10.1016/j.febslet.2010.04.027

10.1038/nrendo.2012.35

Dong F-S , Jiangao S & Ma J , et al. (2012) GPR120 receptor agonists and uses thereof United States Patent Application US 8299117.

10.1038/nm1168

10.1124/mol.111.077388

10.1371/journal.pone.0046300

Saniere, 2102, Azetidine derivatives useful for the treatment of metabolic and inflammatory diseases, International patent application WO 2012/098033 A1

10.4049/jimmunol.0900063

10.1021/jm300215x

10.1097/MOG.0b013e328340076f

10.1038/nature08530

10.1124/jpet.111.187708

10.1016/j.cell.2010.07.041

10.1016/j.cmet.2012.06.006

10.1016/j.cbpb.2009.08.005

10.1210/en.2008-0059

10.1371/journal.pone.0021205

10.1074/jbc.M705077200

10.2741/3589

10.1097/MCO.0b013e328348c06d

10.1038/nature10798

10.1016/j.febslet.2012.01.001

10.1074/jbc.M608019200

Ma, 2010, Aryl GPR120 receptor agonists and uses thereof, United States Patent Application 20100216827

Thông tin
Thông tin xuất bản

British Journal of Nutrition

Tập 111 Số S1

S3-S7

Thông tin tác giả