Intestinal Farnesoid X Receptor Signaling Modulates Metabolic Disease

Digestive Diseases

Volumn 35, Issue 3, 2017, Pages 178-184

  Gonzalez, Frank J ^a   Jiang, Changtao ^c   Xie, Cen ^a   Patterson, Andrew D ^b  

^a NATIONAL CANCER INSTITUTE   (United States)

^b PENNSYLVANIA STATE UNIVERSITY   (United States)

^c PEKING UNIVERSITY HEALTH SCIENCE CENTER   (China)

Author keywords

Bile acids; Ceramides; Diabetes; Farnesoid X receptor; Non alcoholic fatty liver disease; Obesity

Indexed keywords

CERAMIDE; CHENODEOXYCHOLIC ACID; CHOLIC ACID; FARNESOID X RECEPTOR; FIBROBLAST GROWTH FACTOR; CELL RECEPTOR; FARNESOID X-ACTIVATED RECEPTOR;

16S RRNA GENE; ARTICLE; BILIARY CIRRHOSIS; DIABETES MELLITUS; DRUG SAFETY; ENTEROHEPATIC CIRCULATION; GENE; GENE EXPRESSION; HUMAN; METABOLIC DISORDER; NONALCOHOLIC FATTY LIVER; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; BACTERIUM; INTESTINE; METABOLISM; MOLECULARLY TARGETED THERAPY; SIGNAL TRANSDUCTION;

ANIMALS; BACTERIA; HUMANS; INTESTINES; METABOLIC DISEASES; MOLECULAR TARGETED THERAPY; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SIGNAL TRANSDUCTION;

EID: 85014708925     PISSN: 02572753     EISSN: 14219875     Source Type: Journal    
DOI: 10.1159/000450908     Document Type: Article

References (36)

1. Seol W, Choi HS, Moore DD: Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors. Mol Endocrinol 1995; 9: 72-85.
2. Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, Evans RM, Weinberger C: Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 1995; 81: 687-693.
3. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM: Bile acids: natural ligands for an orphan nuclear receptor. Science 1999; 284: 1365-1368.
4. Suh JM, Yu CT, Tang K, Tanaka T, Kodama T, Tsai MJ, Tsai SY: The expression profiles of nuclear receptors in the developing and adult kidney. Mol Endocrinol 2006; 20: 3412-3420.
5. Jiang T, Wang XX, Scherzer P, Wilson P, Tallman J, Takahashi H, Li J, Iwahashi M, Sutherland E, Arend L, Levi M: Farnesoid X receptor modulates renal lipid metabolism, fibrosis, and diabetic nephropathy. Diabetes 2007; 56: 2485-2493.
6. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ: Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 2000; 102: 731-744.
7. Zhang Y, Hagedorn CH, Wang L: Role of nuclear receptor SHP in metabolism and cancer. Biochim Biophys Acta 2011; 1812: 893-908.
8. Dawson PA: Role of the intestinal bile acid transporters in bile acid and drug disposition. Handb Exp Pharmacol 2011; 201: 169-203.
9. Kliewer SA, Mangelsdorf DJ: Bile acids as hormones: the FXR-FGF15/19 pathway. Dig Dis 2015; 33: 327-331.
10. Choi M, Moschetta A, Bookout AL, Peng L, Umetani M, Holmstrom SR, Suino-Powell K, Xu HE, Richardson JA, Gerard RD, Mangelsdorf DJ, Kliewer SA: Identification of a hormonal basis for gallbladder filling. Nat Med 2006; 12: 1253-1255.
11. Aqel B, DiBaise JK: Role of the gut microbiome in nonalcoholic fatty liver disease. Nutr Clin Pract 2015; 30: 780-786.
12. Boursier J, Diehl AM: Implication of gut microbiota in nonalcoholic fatty liver disease. PLoS Pathog 2015; 11:e1004559.
13. Arora T, Backhed F: The gut microbiota and metabolic disease: current understanding and future perspectives. J Intern Med 2016; 280: 339-349.
14. Mitchell JB, Xavier S, DeLuca AM, Sowers AL, Cook JA, Krishna MC, Hahn SM, Russo A: A low molecular weight antioxidant decreases weight and lowers tumor incidence. Free Radic Biol Med 2003; 34: 93-102.
15. Li F, Pang X, Krausz KW, Jiang C, Chen C, Cook JA, Krishna MC, Mitchell JB, Gonzalez FJ, Patterson AD: Stable isotope-and mass spectrometry-based metabolomics as tools in drug metabolism: a study expanding tempol pharmacology. J Proteome Res 2013; 12: 1369-1376.
16. Li F, Jiang C, Krausz KW, Li Y, Albert I, Hao H, Fabre KM, Mitchell JB, Patterson AD, Gonzalez FJ: Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat Commun 2013; 4: 2384.
17. Jiang C, Xie C, Li F, Zhang L, Nichols RG, Krausz KW, Cai J, Qi Y, Fang ZZ, Takahashi S, Tanaka N, Desai D, Amin SG, Albert I, Patterson AD, Gonzalez FJ: Intestinal farnesoid x receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest 2015; 125: 386-402.
18. Unger RH: Lipotoxic diseases. Annu Rev Med 2002; 53: 319-336.
19. Chaurasia B, Summers SA: Ceramides-lipotoxic inducers of metabolic disorders. Trends Endocrinol Metab 2015; 26: 538-550.
20. Kremer GJ, Atzpodien W, Schnellbacher E: Plasma glycosphingolipids in diabetics and normals. Klin Wochenschr 1975; 53: 637-638.
21. Promrat K, Longato L, Wands JR, de la Monte SM: Weight loss amelioration of non-alcoholic steatohepatitis linked to shifts in hepatic ceramide expression and serum ceramide levels. Hepatol Res 2011; 41: 754-762.
22. Ahammed SK, Chowdhury A: Insulin resistance and 'lipotoxic liver diseases'. Trop Gastroenterol 2013; 34: 1-4.
23. Holland WL, Adams AC, Brozinick JT, Bui HH, Miyauchi Y, Kusminski CM, Bauer SM, Wade M, Singhal E, Cheng CC, Volk K, Kuo MS, Gordillo R, Kharitonenkov A, Scherer PE: An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab 2013; 17: 790-797.
24. Cohen P, Spiegelman BM: Brown and beige fat: molecular parts of a thermogenic machine. Diabetes 2015; 64: 2346-2351.
25. Jiang C, Xie C, Lv Y, Li J, Krausz KW, Shi J, Brocker CN, Desai D, Amin SG, Bisson WH, Liu Y, Gavrilova O, Patterson AD, Gonzalez FJ: Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat Commun 2015; 6: 10166.
26. Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, Morelli A, Parks DJ, Willson TM: 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem 2002; 45: 3569-3572.
27. Copple BL, Li T: Pharmacology of bile acid receptors: evolution of bile acids from simple detergents to complex signaling molecules. Pharmacol Res 2016; 104: 9-21.
28. Sanyal AJ: Use of farnesoid X receptor agonists to treat nonalcoholic fatty liver disease. Dig Dis 2015; 33: 426-432.
29. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E; NASH Clinical Research Network: Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 2015; 385: 956-965.
30. Silveira MG, Lindor KD: Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis. Expert Opin Pharmacother 2014; 15: 365-372.
31. Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, Atkins AR, Khvat A, Schnabl B, Yu RT, Brenner DA, Coulter S, Liddle C, Schoonjans K, Olefsky JM, Saltiel AR, Downes M, Evans RM: Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med 2015; 21: 159-165.
32. Cheng Q, Inaba Y, Lu P, Xu M, He J, Zhao Y, Guo GL, Kuruba R, de la Vega R, Evans RW, Li S, Xie W: Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity. Mol Endocrinol 2015; 29: 571-582.
33. Kim I, Morimura K, Shah Y, Yang Q, Ward JM, Gonzalez FJ: Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 2007; 28: 940-946.
34. Yang F, Huang X, Yi T, Yen Y, Moore DD, Huang W: Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res 2007; 67: 863-867.
35. Maran RR, Thomas A, Roth M, Sheng Z, Esterly N, Pinson D, Gao X, Zhang Y, Ganapathy V, Gonzalez FJ, Guo GL: Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J Pharmacol Exp Ther 2009; 328: 469-477.
36. Kong B, Zhu Y, Li G, Williams JA, Buckley K, Tawfik O, Luyendyk JP, Guo GL: Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis. Am J Physiol Gastrointest Liver Physiol 2016; 310:G295-G302.