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Current Diabetes Reports
Published in: Current Diabetes Reports 9/2020

01-09-2020 | Obesity | Pathogenesis of Type 2 Diabetes and Insulin Resistance (ME Patti, Section Editor)

The Physiological Importance of Bile Acid Structure and Composition on Glucose Homeostasis

Author: Sei Higuchi

Published in: Current Diabetes Reports | Issue 9/2020

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Abstract

Purpose of Review

Studies have identified several effects of bile acids (BAs) in glucose homeostasis, energy expenditure, and body weight control, through receptor-dependent and independent mechanisms. BAs are produced from cholesterol and characterized by their structures, which result from enzymes in the liver and the gut microbiota. The aim of this review is to characterize the effects of BA structure and composition on diabetes.

Recent Findings

The hydroxyl groups of BAs interact with binding pockets of receptors and enzymes that affect glucose homeostasis. Human and animal studies show that BA composition is associated with insulin resistance and food intake regulation.

Summary

The hydroxylation of BAs and BA composition contributes to glucose regulation. Modulation of BA composition has the potential to improve glucose metabolism.
Literature
1.
Li F, Jiang C, Krausz KW, Li Y, Albert I, Hao H, et al. Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat Commun. 2013;4:2384.PubMedPubMedCentral
2.
•• Jiang C, Xie C, Lv Y, Li J, Krausz KW, Shi J, et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat Commun. 2015;6:10166. Antagonization of FXR by muricholic acid (MCA) improves insulin homeostasis by decreasing ceramide.PubMedPubMedCentral
3.
Xie C, Jiang C, Shi J, Gao X, Sun D, Sun L, et al. An intestinal farnesoid X receptor-ceramide signaling axis modulates hepatic gluconeogenesis in mice. Diabetes. 2017;66(3):613–26.PubMed
4.
Yuan Y, Wang QY, Zhang J, Nie J, Zhou CG, Yi WQ, et al. A new bile acid from the traditional chinese medicine shedan. J Asian Nat Prod Res. 2019:1–7.
5.
Paumgartner G, Beuers U. Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease. Clin Liver Dis. 2004;8(1):67–81 vi.PubMed
6.
Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313(5790):1137–40.PubMedPubMedCentral
7.
Kars M, Yang L, Gregor MF, Mohammed BS, Pietka TA, Finck BN, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010;59(8):1899–905.PubMedPubMedCentral
8.
•• Magotti P, Bauer I, Igarashi M, Babagoli M, Marotta R, Piomelli D, et al. Structure of human N-acylphosphatidylethanolamine-hydrolyzing phospholipase D: regulation of fatty acid ethanolamide biosynthesis by bile acids. Structure. 2015;23(3):598–604. These results showed that deoxycholic acid binds binding pockets of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D for enzyme activity. This enzyme activity associates with bioactive lipid production.PubMedPubMedCentral
9.
Margheritis E, Castellani B, Magotti P, Peruzzi S, Romeo E, Natali F, et al. Bile acid recognition by NAPE-PLD. ACS Chem Biol. 2016;11(10):2908–14.PubMedPubMedCentral
10.
Pathak P, Xie C, Nichols RG, Ferrell JM, Boehme S, Krausz KW, et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology. 2018;68(4):1574–88.PubMedPubMedCentral
11.
Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A. 2006;103(4):1006–11.PubMedPubMedCentral
12.
Cariou B, van Harmelen K, Duran-Sandoval D, van Dijk TH, Grefhorst A, Abdelkarim M, et al. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem. 2006;281(16):11039–49.PubMed
13.
Ma K, Saha PK, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116(4):1102–9.PubMedPubMedCentral
14.
van Dijk TH, Grefhorst A, Oosterveer MH, Bloks VW, Staels B, Reijngoud DJ, et al. An increased flux through the glucose 6-phosphate pool in enterocytes delays glucose absorption in Fxr−/− mice. J Biol Chem. 2009;284(16):10315–23.PubMedPubMedCentral
15.
Pathak P, Liu H, Boehme S, Xie C, Krausz KW, Gonzalez F, et al. Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism. J Biol Chem. 2017;292(26):11055–69.PubMedPubMedCentral
16.
Stayrook KR, Bramlett KS, Savkur RS, Ficorilli J, Cook T, Christe ME, et al. Regulation of carbohydrate metabolism by the farnesoid X receptor. Endocrinology. 2005;146(3):984–91.PubMed
17.
Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM, et al. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002;296(5571):1313–6.PubMed
18.
Ishizawa M, Akagi D, Makishima M. Lithocholic acid is a vitamin D receptor ligand that acts preferentially in the ileum. Int J Mol Sci. 2018;19(7).
19.
Ishizawa M, Matsunawa M, Adachi R, Uno S, Ikeda K, Masuno H, et al. Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia. J Lipid Res. 2008;49(4):763–72.PubMed
20.
Ni W, Glenn DJ, Gardner DG. Tie-2Cre mediated deletion of the vitamin D receptor gene leads to improved skeletal muscle insulin sensitivity and glucose tolerance. J Steroid Biochem Mol Biol. 2016;164:281–6.PubMed
21.
Oh J, Riek AE, Darwech I, Funai K, Shao J, Chin K, et al. Deletion of macrophage vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice. Cell Rep. 2015;10(11):1872–86.PubMedPubMedCentral
22.
Ozeki J, Choi M, Endo-Umeda K, Sakurai K, Amano S, Makishima M. Enhanced transcription of pancreatic peptide YY by 1alpha-hydroxyvitamin D3 administration in streptozotocin-induced diabetic mice. Neuropeptides. 2013;47(5):329–32.PubMed
23.
Zhang Y, Li H, Guo H, Li B, Zhao Z, Wang P, et al. Genome analysis reveals a synergistic mechanism of ursodeoxycholic acid and jasminoidin in mice brain repair after ischemia/reperfusion: crosstalk among muti-pathways. Front Pharmacol. 2019;10:1383.PubMedPubMedCentral
24.
Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484–9.PubMed
25.
Kumar DP, Rajagopal S, Mahavadi S, Mirshahi F, Grider JR, Murthy KS, et al. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic beta cells. Biochem Biophys Res Commun. 2012;427(3):600–5.PubMedPubMedCentral
26.
Porez G, Prawitt J, Gross B, Staels B. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J Lipid Res. 2012;53(9):1723–37.PubMedPubMedCentral
27.
Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005;329(1):386–90.PubMed
28.
Kuhre RE, Wewer Albrechtsen NJ, Larsen O, Jepsen SL, Balk-Moller E, Andersen DB, et al. Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas. Mol Metab. 2018;11:84–95.PubMedPubMedCentral
29.
Lasalle M, Hoguet V, Hennuyer N, Leroux F, Piveteau C, Belloy L, et al. Topical intestinal aminoimidazole agonists of G-protein-coupled bile acid receptor 1 promote glucagon like peptide-1 secretion and improve glucose tolerance. J Med Chem. 2017;60(10):4185–211.PubMed
30.
Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167–77.PubMedPubMedCentral
31.
Bala V, Rajagopal S, Kumar DP, Nalli AD, Mahavadi S, Sanyal AJ, et al. Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid receptor TGR5 is mediated by Epac/PLC-epsilon pathway and modulated by endogenous H2S. Front Physiol. 2014;5:420.PubMedPubMedCentral
32.
Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284(5418):1362–5.PubMed
33.
Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999;284(5418):1365–8.PubMed
34.
Wang H, Chen J, Hollister K, Sowers LC, Forman BM. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell. 1999;3(5):543–53.PubMed
35.
Zhang Y, Kast-Woelbern HR, Edwards PA. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J Biol Chem. 2003;278(1):104–10.PubMed
36.
Huber RM, Murphy K, Miao B, Link JR, Cunningham MR, Rupar MJ, et al. Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters. Gene. 2002;290(1–2):35–43.PubMed
37.
Bishop-Bailey D, Walsh DT, Warner TD. Expression and activation of the farnesoid X receptor in the vasculature. Proc Natl Acad Sci U S A. 2004;101(10):3668–73.PubMedPubMedCentral
38.
Cipriani S, Mencarelli A, Palladino G, Fiorucci S. FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res. 2010;51(4):771–84.PubMedPubMedCentral
39.
•• Higuchi S, Ahmad TR, Argueta DA, Perez PA, Zhao C, Schwartz GJ, et al. Bile acid composition regulates GPR119-dependent intestinal lipid sensing and food intake regulation in mice. Gut. 2020:gutjnl-2019-319693. This study provides that lowering 12α-hydroxylated bile acids induces slow gastric emptying and low food inake by lipid sensing receptor GPR119 activation.
40.
•• Kaur A, Patankar JV, de Haan W, Ruddle P, Wijesekara N, Groen AK, et al. Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1. Diabetes. 2015;64(4):1168–79. This study indicated that lowering 12α-hydroxylated bile acids improve glucose homeostasis.PubMed
41.
•• Bertaggia E, Jensen KK, Castro-Perez J, Xu Y, Di Paolo G, Chan RB, et al. Cyp8b1 ablation prevents western diet-induced weight gain and hepatic steatosis due to impaired fat absorption. Am J Physiol Endocrinol Metab. 2017;ajpendo 00409 2016. The results show that lowering 12α-hydroxylated bile acids improve glucose homeostasis because of impaired lipid absorption.
42.
Haeusler RA, Pratt-Hyatt M, Welch CL, Klaassen CD, Accili D. Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia. Cell Metab. 2012;15(1):65–74.PubMed
43.
Haeusler RA, Astiarraga B, Camastra S, Accili D, Ferrannini E. Human insulin resistance is associated with increased plasma levels of 12alpha-hydroxylated bile acids. Diabetes. 2013;62(12):4184–91.PubMedPubMedCentral
44.
•• Haeusler RA, Camastra S, Nannipieri M, Astiarraga B, Castro-Perez J, Xie D, et al. Increased bile acid synthesis and impaired bile acid transport in human obesity. J Clin Endocrinol Metab. 2016;101(5):1935–44. This study revealed that bile acid synthesis and 12α-hydroxylation is associated with obesity and type 2 diabetes.PubMed
45.
46.
Hagey LR, Vidal N, Hofmann AF, Krasowski MD. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites. BMC Evol Biol. 2010;10:133.PubMedPubMedCentral
47.
Takahashi S, Fukami T, Masuo Y, Brocker CN, Xie C, Krausz KW, et al. Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans. J Lipid Res. 2016;57(12):2130–7.PubMedPubMedCentral
48.
de Boer JF, Verkade E, Mulder NL, de Vries HD, Huijkman NC, Koehorst M, et al. A human-like bile acid pool induced by deletion of Cyp2c70 modulates effects of farnesoid X receptor activation in mice. J Lipid Res. 2019.
49.
Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002;298(5):714–9.PubMed
50.
Vassileva G, Golovko A, Markowitz L, Abbondanzo SJ, Zeng M, Yang S, et al. Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem J. 2006;398(3):423–30.PubMedPubMedCentral
51.
Mussig K, Staiger H, Machicao F, Machann J, Schick F, Schafer SA, et al. Preliminary report: genetic variation within the GPBAR1 gene is not associated with metabolic traits in white subjects at an increased risk for type 2 diabetes mellitus. Metabolism. 2009;58(12):1809–11.PubMed
52.
Briere DA, Ruan X, Cheng CC, Siesky AM, Fitch TE, Dominguez C, et al. Novel small molecule agonist of TGR5 possesses anti-diabetic effects but causes gallbladder filling in mice. PLoS One. 2015;10(8):e0136873.PubMedPubMedCentral
53.
Cao H, Chen ZX, Wang K, Ning MM, Zou QA, Feng Y, et al. Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect. Sci Rep. 2016;6:28676.PubMedPubMedCentral
54.
Duan H, Ning M, Zou Q, Ye Y, Feng Y, Zhang L, et al. Discovery of intestinal targeted TGR5 agonists for the treatment of type 2 diabetes. J Med Chem. 2015;58(8):3315–28.PubMed
55.
Alemi F, Kwon E, Poole DP, Lieu T, Lyo V, Cattaruzza F, et al. The TGR5 receptor mediates bile acid-induced itch and analgesia. J Clin Invest. 2013;123(4):1513–30.PubMedPubMedCentral
56.
Hodge RJ, Nunez DJ. The therapeutic potential of TGR5 agonists. Hope or hype? Diabetes Obes Metab. 2016.
57.
Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002;45(17):3569–72.PubMed
58.
Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, et al. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol Cell. 2003;11(4):1093–100.PubMed
59.
Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL, McDonald JG, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2(4):217–25.PubMed
60.
Tomlinson E, Fu L, John L, Hultgren B, Huang X, Renz M, et al. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity. Endocrinology. 2002;143(5):1741–7.PubMed
61.
Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science. 2011;331(6024):1621–4.PubMedPubMedCentral
62.
Fu L, John LM, Adams SH, Yu XX, Tomlinson E, Renz M, et al. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology. 2004;145(6):2594–603.PubMed
63.
Potthoff MJ, Boney-Montoya J, Choi M, He T, Sunny NE, Satapati S, et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1alpha pathway. Cell Metab. 2011;13(6):729–38.PubMedPubMedCentral
64.
Gallego-Escuredo JM, Gomez-Ambrosi J, Catalan V, Domingo P, Giralt M, Fruhbeck G, et al. Opposite alterations in FGF21 and FGF19 levels and disturbed expression of the receptor machinery for endocrine FGFs in obese patients. Int J Obes. 2015;39(1):121–9.
65.
Roesch SL, Styer AM, Wood GC, Kosak Z, Seiler J, Benotti P, et al. Perturbations of fibroblast growth factors 19 and 21 in type 2 diabetes. PLoS One. 2015;10(2):e0116928.PubMedPubMedCentral
66.
Friedrich D, Marschall HU, Lammert F. Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial. BMC Gastroenterol. 2018;18(1):76.PubMedPubMedCentral
67.
Sayin SI, Wahlstrom A, Felin J, Jantti S, Marschall HU, Bamberg K, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013;17(2):225–35.PubMed
68.
Jiang C, Xie C, Li F, Zhang L, Nichols RG, Krausz KW, et al. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest. 2015;125(1):386–402.PubMed
69.
Chaurasia B, Tippetts TS, Mayoral Monibas R, Liu J, Li Y, Wang L, et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science. 2019;365(6451):386–92.PubMedPubMedCentral
70.
71.
Hammerschmidt P, Ostkotte D, Nolte H, Gerl MJ, Jais A, Brunner HL, et al. CerS6-derived sphingolipids interact with Mff and promote mitochondrial fragmentation in obesity. Cell. 2019;177(6):1536–52 e23.PubMed
72.
Raichur S, Wang ST, Chan PW, Li Y, Ching J, Chaurasia B, et al. CerS2 haploinsufficiency inhibits beta-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance. Cell Metab. 2014;20(4):687–95.PubMed
73.
Raichur S, Brunner B, Bielohuby M, Hansen G, Pfenninger A, Wang B, et al. The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach. Mol Metab. 2019;21:36–50.PubMedPubMedCentral
74.
Turpin SM, Nicholls HT, Willmes DM, Mourier A, Brodesser S, Wunderlich CM, et al. Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metab. 2014;20(4):678–86.PubMed
75.
Tagami S, Inokuchi Ji J, Kabayama K, Yoshimura H, Kitamura F, Uemura S, et al. Ganglioside GM3 participates in the pathological conditions of insulin resistance. J Biol Chem. 2002;277(5):3085–92.PubMed
76.
Yamashita T, Hashiramoto A, Haluzik M, Mizukami H, Beck S, Norton A, et al. Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci U S A. 2003;100(6):3445–9.PubMedPubMedCentral
77.
Heuman DM. Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions. J Lipid Res. 1989;30(5):719–30.PubMed
78.
Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev. 2012;33(3):456–92.PubMedPubMedCentral
79.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.PubMed
80.
Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J. 2003;17(3):509–11.PubMed
81.
Upchurch BH, Aponte GW, Leiter AB. Expression of peptide YY in all four islet cell types in the developing mouse pancreas suggests a common peptide YY-producing progenitor. Development. 1994;120(2):245–52.PubMed
82.
Jackerott M, Oster A, Larsson LI. PYY in developing murine islet cells: comparisons to development of islet hormones, NPY, and BrdU incorporation. J Histochem Cytochem. 1996;44(8):809–17.PubMed
83.
Bottcher G, Ekman R, Lundqvist G, Ahren B, Sundler F. Pancreatic peptide YY in alloxan diabetic mice. Pancreas. 1994;9(4):469–74.PubMed
84.
Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzog H, et al. Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab. 2006;4(3):223–33.PubMed
85.
Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002;418(6898):650–4.PubMed
86.
Boey D, Lin S, Enriquez RF, Lee NJ, Slack K, Couzens M, et al. PYY transgenic mice are protected against diet-induced and genetic obesity. Neuropeptides. 2008;42(1):19–30.PubMed
87.
Adachi R, Shulman AI, Yamamoto K, Shimomura I, Yamada S, Mangelsdorf DJ, et al. Structural determinants for vitamin D receptor response to endocrine and xenobiotic signals. Mol Endocrinol. 2004;18(1):43–52.PubMed
88.
Masuno H, Ikura T, Morizono D, Orita I, Yamada S, Shimizu M, et al. Crystal structures of complexes of vitamin D receptor ligand-binding domain with lithocholic acid derivatives. J Lipid Res. 2013;54(8):2206–13.PubMedPubMedCentral
89.
Ikura T, Ito N. Crystal structure of the vitamin D receptor ligand-binding domain with Lithocholic acids. Vitam Horm. 2016;100:117–36.PubMed
90.
Rahman IA, Tsuboi K, Uyama T, Ueda N. New players in the fatty acyl ethanolamide metabolism. Pharmacol Res. 2014;86:1–10.PubMed
91.
Fu J, Astarita G, Gaetani S, Kim J, Cravatt BF, Mackie K, et al. Food intake regulates oleoylethanolamide formation and degradation in the proximal small intestine. J Biol Chem. 2007;282(2):1518–28.PubMed
92.
Schwartz GJ, Fu J, Astarita G, Li X, Gaetani S, Campolongo P, et al. The lipid messenger OEA links dietary fat intake to satiety. Cell Metab. 2008;8(4):281–8.PubMedPubMedCentral
93.
Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A. Rodriguez De Fonseca F et al. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature. 2003;425(6953):90–3.PubMed
94.
Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946–9.
95.
Cota D, Marsicano G, Tschop M, Grubler Y, Flachskamm C, Schubert M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest. 2003;112(3):423–31.PubMedPubMedCentral
96.
Cota D, Tschop MH, Horvath TL, Levine AS. Cannabinoids, opioids and eating behavior: the molecular face of hedonism? Brain Res Rev. 2006;51(1):85–107.PubMed
97.
Mano N, Goto T, Uchida M, Nishimura K, Ando M, Kobayashi N, et al. Presence of protein-bound unconjugated bile acids in the cytoplasmic fraction of rat brain. J Lipid Res. 2004;45(2):295–300.PubMed
98.
Wangensteen T, Akselsen H, Holmen J, Undlien D, Retterstol L. A common haplotype in NAPEPLD is associated with severe obesity in a Norwegian population-based cohort (the HUNT study). Obesity (Silver Spring). 2011;19(3):612–7.
99.
Igarashi M, Narayanaswami V, Kimonis V, Galassetti PM, Oveisi F, Jung KM, et al. Dysfunctional oleoylethanolamide signaling in a mouse model of Prader-Willi syndrome. Pharmacol Res. 2017;117:75–81.PubMed
100.
Igarashi M, DiPatrizio NV, Narayanaswami V, Piomelli D. Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents. Biochim Biophys Acta. 2015;1851(9):1218–26.PubMedPubMedCentral
101.
Fu J, Oveisi F, Gaetani S, Lin E, Piomelli D. Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Neuropharmacology. 2005;48(8):1147–53.PubMed
102.
Hankir MK, Seyfried F, Hintschich CA, Diep TA, Kleberg K, Kranz M, et al. Gastric bypass surgery recruits a gut PPAR-alpha-striatal D1R pathway to reduce fat appetite in obese rats. Cell Metab. 2017;25(2):335–44.PubMed
103.
Ren T, Ma A, Zhuo R, Zhang H, Peng L, Jin X, et al. Oleoylethanolamide increases glycogen synthesis and inhibits hepatic gluconeogenesis via the LKB1/AMPK pathway in type 2 diabetic model. J Pharmacol Exp Ther. 2020;373(1):81–91.PubMed
104.
Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci. 2008;65(16):2461–83.PubMed
105.
Wang DQ, Carey MC. Therapeutic uses of animal biles in traditional Chinese medicine: an ethnopharmacological, biophysical chemical and medicinal review. World J Gastroenterol. 2014;20(29):9952–75.PubMedPubMedCentral
106.
Matsumoto M, Pocai A, Rossetti L, Depinho RA, Accili D. Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. Cell Metab. 2007;6(3):208–16.PubMed
107.
Haeusler RA, Kaestner KH, Accili D. FoxOs function synergistically to promote glucose production. J Biol Chem. 2010;285(46):35245–8.PubMedPubMedCentral
108.
Ishida H, Yamashita C, Kuruta Y, Yoshida Y, Noshiro M. Insulin is a dominant suppressor of sterol 12 alpha-hydroxylase P450 (CYP8B) expression in rat liver: possible role of insulin in circadian rhythm of CYP8B. J Biochem. 2000;127(1):57–64.PubMed
109.
Pathak P, Chiang JYL. Sterol 12alpha-hydroxylase aggravates dyslipidemia by activating the ceramide/mTORC1/SREBP-1C pathway via FGF21 and FGF15. Gene Expr. 2019;19(3):161–73.PubMedPubMedCentral
110.
Biddinger SB, Haas JT, Yu BB, Bezy O, Jing E, Zhang W, et al. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med. 2008;14(7):778–82.PubMedPubMedCentral
111.
Pathak P, Li T, Chiang JY. Retinoic acid-related orphan receptor alpha regulates diurnal rhythm and fasting induction of sterol 12alpha-hydroxylase in bile acid synthesis. J Biol Chem. 2013;288(52):37154–65.PubMedPubMedCentral
112.
Hoogerland JA, Lei Y, Wolters JC, de Boer JF, Bos T, Bleeker A, et al. Glucose-6-phosphate regulates hepatic bile acid synthesis in mice. Hepatology. 2019;70(6):2171–84.PubMedPubMedCentral
113.
Brufau G, Stellaard F, Prado K, Bloks VW, Jonkers E, Boverhof R, et al. Improved glycemic control with colesevelam treatment in patients with type 2 diabetes is not directly associated with changes in bile acid metabolism. Hepatology. 2010;52(4):1455–64.
114.
•• Bonde Y, Eggertsen G, Rudling M. Mice abundant in muricholic bile acids show resistance to dietary induced steatosis, weight gain, and to impaired glucose metabolism. PLoS One. 2016;11(1):e0147772. The results show that lowering 12α-hydroxylated bile acids improve glucose homeostasis because of impaired lipid absorption.PubMedPubMedCentral
115.
Li-Hawkins J, Gafvels M, Olin M, Lund EG, Andersson U, Schuster G, et al. Cholic acid mediates negative feedback regulation of bile acid synthesis in mice. J Clin Invest. 2002;110(8):1191–200.PubMedPubMedCentral
116.
Hansen HS, Rosenkilde MM, Holst JJ, Schwartz TW. GPR119 as a fat sensor. Trends Pharmacol Sci. 2012;33(7):374–81.PubMed
117.
Flock G, Holland D, Seino Y, Drucker DJ. GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms. Endocrinology. 2011;152(2):374–83.PubMed
118.
Odori S, Hosoda K, Tomita T, Fujikura J, Kusakabe T, Kawaguchi Y, et al. GPR119 expression in normal human tissues and islet cell tumors: evidence for its islet-gastrointestinal distribution, expression in pancreatic beta and alpha cells, and involvement in islet function. Metabolism. 2013;62(1):70–8.PubMed
119.
Moss CE, Glass LL, Diakogiannaki E, Pais R, Lenaghan C, Smith DM, et al. Lipid derivatives activate GPR119 and trigger GLP-1 secretion in primary murine L-cells. Peptides. 2016;77:16–20.PubMedPubMedCentral
120.
Mandoe MJ, Hansen KB, Hartmann B, Rehfeld JF, Holst JJ, Hansen HS. The 2-monoacylglycerol moiety of dietary fat appears to be responsible for the fat-induced release of GLP-1 in humans. Am J Clin Nutr. 2015;102(3):548–55.PubMed
121.
Wewalka M, Patti ME, Barbato C, Houten SM, Goldfine AB. Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin. J Clin Endocrinol Metab. 2014;99(4):1442–51.PubMedPubMedCentral
Metadata
Title
The Physiological Importance of Bile Acid Structure and Composition on Glucose Homeostasis
Author
Sei Higuchi
Publication date
01-09-2020
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 9/2020
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-020-01329-5

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