Biomarker Information

Bile Acids

Regulate cholesterol Homeostasis

Bile Acids Analyses Using Tandem Mass Spectrometry

Bile acids are well recognized as essential for regulating cholesterol homeostasis and the digestion and absorption of fat through the intestine.  In recent years, however, bile acids have emerged as crucial signaling molecules with endocrine functions, acting as ligands for the G-protein coupled receptor TGR5 and the nuclear receptor farnesoid X receptor (FXR) resulting in the secretion of GLP-1, PYY and oxyntomodulin from enteroendocrine L-cells.  Hence bile acids decrease blood glucose levels and are anorexigenic through PYY and oxyntomodulin, causing weight loss.  This has elevated the importance of bile acids beyond fat digestion and into triglyceride, cholesterol, and glucose homeostasis.  There is growing interest in bile acids as therapeutic targets for the treatment of obesity, type 2 diabetes, and hyperlipidemia.

The study of bile acid functions requires methods which cover the complexity of this structurally diverse group of molecules.  In recent years a number of methods using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) have been developed, which allow analysis of free and conjugated bile acids without derivatization.  Most other methods have the disadvantage of time consuming extraction procedures, long analysis times and lack of baseline separation for isobaric species.

References

1. Pellicciari RPruzanski MAuwerx JSchoonjans K. Targeting bile-acid signalling for metabolic diseases. Thomas C Nat Rev Drug Discov. 2008 Aug;7(8):678-93.

2. Monte MJMarin JJAntelo AVazquez-Tato J. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol. 2009 Feb 21;15(7):804-16.
3. Katsuma SHirasawa ATsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005 Apr 1;329(1):386-90.
4. Adrian TE, Garibella S, Parekh KA, Thomas SA, Saadi H, Al-Kaabi J, Nagelkerke N, Gedulin B, Young AA. The Bile Acid Brake: A novel target for treating diabetes and obesity. Poster presentation (#602) at the American Diabetes Association 70th Scientific Sessions, June 2010, Orlando, USA.
5.  Yang JIYoon JHMyung SJGwak GYKim WChung GELee SHLee SMKim CYLee HS. Bile acid-induced TGR5-dependent c-Jun-N terminal kinase activation leads to enhanced caspase 8 activation in hepatocytes. Biochem Biophys Res Commun. 2007 Sep 14;361(1):156-61. Epub 2007 Jul 19.
6.  West KLZern TLButteiger DNKeller BTFernandez ML. SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT) inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs. Atherosclerosis. 2003 Dec;171(2):201-10.
7.  Scherer M, Gnewuch C, Schmitz, G, Liebisch G.  Rapid quantification of bile acids and their conjugates in serum by liquid chromatography-tandem mass spectrometry.  J Chromatogr B. 2009; 877:3920-3925.

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