1932

Abstract

Recent research has convincingly demonstrated a bidirectional communication axis between the gut and liver that enables the gut microbiota to strongly affect animals’ feeding behavior and energy metabolism. As such, the gut–liver axis enables the host to control and shape the gut microbiota and to protect the intestinal barrier. Gut microbiota–host communication is based on several gut-derived compounds, such as short-chain fatty acids, bile acids, methylamines, amino acid–derived metabolites, and microbial-associated molecular patterns, which act as communication signals, and multiple host receptors, which sense the signals, thereby stimulating signaling and metabolic pathways in all key tissues of energy metabolism and food intake regulation. Disturbance in the microbial ecosystem balance, or microbial dysbiosis, causes profound derangements in the regulation of appetite and satiety in the hypothalamic centers of the brain and in key metabolic pathways in peripheral tissues owing to intestinal barrier disruption and subsequent induction of hepatic and hypothalamic inflammation.

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2020-02-15
2024-04-24
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Literature Cited

  1. 1. 
    Brandl K, Kumar V, Eckmann L 2017. Gut-liver axis at the frontier of host-microbial interactions. Am. J. Physiol. Gastrointest. Liver Physiol. 312:G413–19
    [Google Scholar]
  2. 2. 
    Turner JR. 2009. Intestinal mucosal barrier function in health and disease. Nat. Rev. Immunol. 9:799–809
    [Google Scholar]
  3. 3. 
    Abreu MT. 2010. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat. Rev. Immunol. 10:131–44
    [Google Scholar]
  4. 4. 
    Mantis NJ, Rol N, Corthésy B 2011. Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 4:603–11
    [Google Scholar]
  5. 5. 
    Balmer ML, Slack E, de Gottardi A, Lawson MA, Hapfelmeier S et al. 2014. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci. Transl. Med. 6:237ra66
    [Google Scholar]
  6. 6. 
    Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY et al. 2004. The gut microbiota as an environmental factor that regulates fat storage. PNAS 101:15718–23
    [Google Scholar]
  7. 7. 
    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–31
    [Google Scholar]
  8. 8. 
    Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI 2007. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. PNAS 104:979–84
    [Google Scholar]
  9. 9. 
    Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL et al. 2005. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab 2:217–25
    [Google Scholar]
  10. 10. 
    Mirpuri J, Raetz M, Sturge CR, Wilhelm CL, Benson A et al. 2014. Proteobacteria-specific IgA regulates maturation of the intestinal microbiota. Gut Microbes 5:28–39
    [Google Scholar]
  11. 11. 
    Moro-Sibilot L, Blanc P, Taillardet M, Bardel E, Couillault C et al. 2016. Mouse and human liver contain immunoglobulin A-secreting cells originating from Peyer's patches and directed against intestinal antigens. Gastroenterology 151:311–23
    [Google Scholar]
  12. 12. 
    Joly-Amado A, Cansell C, Denis RG, Delbes AS, Castel J et al. 2014. The hypothalamic arcuate nucleus and the control of peripheral substrates. Best Pract. Res. Clin. Endocrinol. Metab. 28:725–37
    [Google Scholar]
  13. 13. 
    Millington GW. 2007. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr. Metab. 4:18
    [Google Scholar]
  14. 14. 
    Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD 1999. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron 24:155–63
    [Google Scholar]
  15. 15. 
    Theodorakis MJ, Carlson O, Michopoulos S, Doyle ME, Juhaszova M et al. 2006. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am. J. Physiol. Endocrinol. Metab. 290:E550–59
    [Google Scholar]
  16. 16. 
    Cummings DE. 2006. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol. Behav. 89:71–84
    [Google Scholar]
  17. 17. 
    Cone RD, Cowley MA, Butler AA, Fan W, Marks DL, Low MJ 2001. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int. J. Obes. Relat. Metab. Disord. 25:Suppl. 5S63–67
    [Google Scholar]
  18. 18. 
    Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D et al. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540–43
    [Google Scholar]
  19. 19. 
    Chien EK, Hara M, Rouard M, Yano H, Phillippe M et al. 1997. Increase in serum leptin and uterine leptin receptor messenger RNA levels during pregnancy in rats. Biochem. Biophys. Res. Commun. 237:476–80
    [Google Scholar]
  20. 20. 
    Ehrhardt RA, Slepetis RM, Bell AW, Boisclair YR 2001. Maternal leptin is elevated during pregnancy in sheep. Domest. Anim. Endocrinol. 21:85–96
    [Google Scholar]
  21. 21. 
    Grattan DR, Ladyman SR, Augustine RA 2007. Hormonal induction of leptin resistance during pregnancy. Physiol. Behav. 91:366–74
    [Google Scholar]
  22. 22. 
    Clarke IJ, Tilbrook AJ, Turner AI, Doughton BW, Goding JW 2001. Sex, fat and the tilt of the earth: effects of sex and season on the feeding response to centrally administered leptin in sheep. Endocrinology 142:2725–28
    [Google Scholar]
  23. 23. 
    Miller DW, Findlay PA, Morrison MA, Raver N, Adam CL 2002. Seasonal and dose-dependent effects of intracerebroventricular leptin on LH secretion and appetite in sheep. J. Endocrinol. 175:395–404
    [Google Scholar]
  24. 24. 
    Klingenspor M, Niggemann H, Heldmaier G 2000. Modulation of leptin sensitivity by short photoperiod acclimation in the Djungarian hamster. Phodopus sungorus. J. Comp. Physiol. B 170:37–43
    [Google Scholar]
  25. 25. 
    Bernabucci U, Basiricò L, Lacetera N, Morera P, Ronchi B et al. 2006. Photoperiod affects gene expression of leptin and leptin receptors in adipose tissue from lactating dairy cows. J. Dairy Sci. 89:4678–86
    [Google Scholar]
  26. 26. 
    Cavuoto P, Wittert GA. 2009. The role of the endocannabinoid system in the regulation of energy expenditure. Best Pract. Res. Clin. Endocrinol. Metab. 23:79–86
    [Google Scholar]
  27. 27. 
    Di Marzo V, Goparaju SK, Wang L, Liu J, Bátkai S et al. 2001. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410:822–25
    [Google Scholar]
  28. 28. 
    Ravinet Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P et al. 2003. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284:R345–53
    [Google Scholar]
  29. 29. 
    Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S et al. 2005. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J. Clin. Investig. 115:1298–305
    [Google Scholar]
  30. 30. 
    Matias I, Di Marzo V 2007. Endocannabinoids and the control of energy balance. Trends Endocrinol. Metab. 18:27–37
    [Google Scholar]
  31. 31. 
    Silvestri C, Ligresti A, Di Marzo V 2011. Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle. Rev. Endocr. Metab. Disord. 12:153–62
    [Google Scholar]
  32. 32. 
    Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D et al. 1995. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur. J. Biochem. 232:54–61
    [Google Scholar]
  33. 33. 
    Cristino L, Palomba L, Di Marzo V 2014. New horizons on the role of cannabinoid CB1 receptors in palatable food intake, obesity and related dysmetabolism. Int. J. Obes. Suppl. 4:Suppl. 1S26–30
    [Google Scholar]
  34. 34. 
    Colombo G, Agabio R, Diaz G, Lobina C, Reali R, Gessa GL 1998. Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci 63:PL113–17
    [Google Scholar]
  35. 35. 
    Cota D, Marsicano G, Tschöp M, Grübler Y, Flachskamm C et al. 2003. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J. Clin. Investig. 112:423–31
    [Google Scholar]
  36. 36. 
    Simiand J, Keane M, Keane PE, Soubrié P 1998. SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Behav. Pharmacol. 9:179–81
    [Google Scholar]
  37. 37. 
    Cluny NL, Vemuri VK, Chambers AP, Limebeer CL, Bedard H et al. 2010. A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents. Br. J. Pharmacol. 161:629–42
    [Google Scholar]
  38. 38. 
    Artegoitia VM, Foote AP, Lewis RM, King DA, Shackelford SD et al. 2016. Endocannabinoids concentrations in plasma associated with feed efficiency and carcass composition of beef steers. J. Anim. Sci. 94:5177–81
    [Google Scholar]
  39. 39. 
    Artegoitia VM, Foote AP, Tait RG, Kuehn LA, Lewis RM et al. 2017. Endocannabinoid concentrations in plasma during the finishing period are associated with feed efficiency and carcass composition of beef cattle. J. Anim. Sci. 95:4568–74
    [Google Scholar]
  40. 40. 
    Khan MJ, Graugnard DE, Loor JJ 2012. Endocannabinoid system and proopiomelanocortin gene expression in peripartal bovine liver in response to prepartal plane of nutrition. J. Anim. Physiol. Anim. Nutr. 96:907–19
    [Google Scholar]
  41. 41. 
    Zachut M, Kra G, Moallem U, Livshitz L, Levin Y et al. 2018. Characterization of the endocannabinoid system in subcutaneous adipose tissue in periparturient dairy cows and its association to metabolic profiles. PLOS ONE 13:e0205996
    [Google Scholar]
  42. 42. 
    Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM et al. 2010. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 6:392
    [Google Scholar]
  43. 43. 
    Karaliota S, Siafaka-Kapadai A, Gontinou C, Psarra K, Mavri-Vavayanni M 2009. Anandamide increases the differentiation of rat adipocytes and causes PPARγ and CB1 receptor upregulation. Obesity 17:1830–38
    [Google Scholar]
  44. 44. 
    Bouaboula M, Hilairet S, Marchand J, Fajas L, Le Fur G, Casellas P 2005. Anandamide induced PPARγ transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur. J. Pharmacol. 517:174–81
    [Google Scholar]
  45. 45. 
    Tedesco L, Valerio A, Dossena M, Cardile A, Ragni M et al. 2010. Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: the role of eNOS, p38 MAPK, and AMPK pathways. Diabetes 59:2826–36
    [Google Scholar]
  46. 46. 
    Matias I, Gonthier MP, Orlando P, Martiadis V, De Petrocellis L et al. 2006. Regulation, function, and dysregulation of endocannabinoids in models of adipose and β-pancreatic cells and in obesity and hyperglycemia. J. Clin. Endocrinol. Metab. 91:3171–80
    [Google Scholar]
  47. 47. 
    Tedesco L, Valerio A, Cervino C, Cardile A, Pagano C et al. 2008. Cannabinoid type 1 receptor blockade promotes mitochondrial biogenesis through endothelial nitric oxide synthase expression in white adipocytes. Diabetes 57:2028–36
    [Google Scholar]
  48. 48. 
    Ruiz de Azua I, Mancini G, Srivastava RK, Rey AA, Cardinal P et al. 2017. Adipocyte cannabinoid receptor CB1 regulates energy homeostasis and alternatively activated macrophages. J. Clin. Investig. 127:4148–62
    [Google Scholar]
  49. 49. 
    Mehrpouya-Bahrami P, Chitrala KN, Ganewatta MS, Tang C, Murphy EA et al. 2017. Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity. Sci. Rep. 7:15645
    [Google Scholar]
  50. 50. 
    Maccarrone M, De Petrocellis L, Bari M, Fezza F, Salvati S et al. 2001. Lipopolysaccharide downregulates fatty acid amide hydrolase expression and increases anandamide levels in human peripheral lymphocytes. Arch. Biochem. Biophys. 393:321–28
    [Google Scholar]
  51. 51. 
    Liu J, Batkai S, Pacher P, Harvey-White J, Wagner JA et al. 2003. Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-κB independently of platelet-activating factor. J. Biol. Chem. 278:45034–39
    [Google Scholar]
  52. 52. 
    Osei-Hyiaman D, Liu J, Zhou L, Godlewski G, Harvey-White J et al. 2008. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J. Clin. Investig. 118:3160–69
    [Google Scholar]
  53. 53. 
    Bradford BJ, Yuan K, Farney JK, Mamedova LK, Carpenter AJ 2015. Invited review: inflammation during the transition to lactation: new adventures with an old flame. J. Dairy Sci. 98:6631–50
    [Google Scholar]
  54. 54. 
    Bionaz M, Trevisi E, Calamari L, Librandi F, Ferrari A, Bertoni G 2007. Plasma paraoxonase, health, inflammatory conditions, and liver function in transition dairy cows. J. Dairy Sci. 90:1740–50
    [Google Scholar]
  55. 55. 
    Zebeli Q, Metzler-Zebeli BU. 2012. Interplay between rumen digestive disorders and diet-induced inflammation in dairy cattle. Res. Vet. Sci. 93:1099–108
    [Google Scholar]
  56. 56. 
    Ringseis R, Gessner DK, Eder K 2015. Molecular insights into the mechanisms of liver-associated diseases in early-lactating dairy cows: hypothetical role of endoplasmic reticulum stress. J. Anim. Physiol. Anim. Nutr. 99:626–45
    [Google Scholar]
  57. 57. 
    Zhu Y, Guan Y, Loor JJ, Sha X, Coleman DN et al. 2019. Fatty acid-induced endoplasmic reticulum stress promoted lipid accumulation in calf hepatocytes, and endoplasmic reticulum stress existed in the liver of severe fatty liver cows. J. Dairy Sci. 102:7359–70
    [Google Scholar]
  58. 58. 
    Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ 2006. Colonic health: fermentation and short chain fatty acids. J. Clin. Gastroenterol. 40:235–43
    [Google Scholar]
  59. 59. 
    Frankel WL, Zhang W, Singh A, Klurfeld DM, Don S et al. 1994. Mediation of the trophic effects of short-chain fatty acids on the rat jejunum and colon. Gastroenterology 106:375–80
    [Google Scholar]
  60. 60. 
    Bloemen JG, Venema K, van de Poll MC, Olde Damink SW, Buurman WA, Dejong CH 2009. Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clin. Nutr. 28:657–61
    [Google Scholar]
  61. 61. 
    Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L et al. 2003. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278:11312–19
    [Google Scholar]
  62. 62. 
    Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP et al. 2009. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res 69:2826–32
    [Google Scholar]
  63. 63. 
    Aguinaga Casañas MA, Schäff CT, Albrecht E, Hammon HM, Kuhla B et al. 2017. Short communication: free fatty acid receptors FFAR1 and FFAR2 during the peripartal period in liver of dairy cows grouped by their postpartum plasma β-hydroxybutyrate concentrations. J. Dairy Sci. 100:3287–92
    [Google Scholar]
  64. 64. 
    Friedrichs P, Saremi B, Winand S, Rehage J, Dänicke S et al. 2014. Energy and metabolic sensing G protein-coupled receptors during lactation-induced changes in energy balance. Domest. Anim. Endocrinol. 48:33–41
    [Google Scholar]
  65. 65. 
    Friedrichs P, Sauerwein H, Huber K, Locher LF, Rehage J et al. 2016. Expression of metabolic sensing receptors in adipose tissues of periparturient dairy cows with differing extent of negative energy balance. Animal 10:623–32
    [Google Scholar]
  66. 66. 
    Xiong Y, Miyamoto N, Shibata K, Valasek MA, Motoike T et al. 2004. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. PNAS 101:1045–50
    [Google Scholar]
  67. 67. 
    Soliman M, Kimura K, Ahmed M, Yamaji D, Matsushita Y et al. 2007. Inverse regulation of leptin mRNA expression by short- and long-chain fatty acids in cultured bovine adipocytes. Domest. Anim. Endocrinol. 33:400–9
    [Google Scholar]
  68. 68. 
    Lee SH, Hossner KL. 2002. Coordinate regulation of ovine adipose tissue gene expression by propionate. J. Anim. Sci. 80:2840–49
    [Google Scholar]
  69. 69. 
    Jiao AR, Diao H, Yu B, He J, Yu J et al. 2018. Oral administration of short chain fatty acids could attenuate fat deposition of pigs. PLOS ONE 13:e0196867
    [Google Scholar]
  70. 70. 
    Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S et al. 2014. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 5:3611
    [Google Scholar]
  71. 71. 
    Jiang L, Gulanski BI, De Feyter HM, Weinzimer SA, Pittman B et al. 2013. Increased brain uptake and oxidation of acetate in heavy drinkers. J. Clin. Investig. 123:1605–14
    [Google Scholar]
  72. 72. 
    Cherbut C, Ferrier L, Rozé C, Anini Y, Blottière H et al. 1998. Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am. J. Physiol. 275:G1415–22
    [Google Scholar]
  73. 73. 
    Cuche G, Cuber JC, Malbert CH 2000. Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 279:G925–30
    [Google Scholar]
  74. 74. 
    Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM et al. 2012. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLOS ONE 7:e35240
    [Google Scholar]
  75. 75. 
    Cani PD, Dewever C, Delzenne NM 2004. Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats. Br. J. Nutr. 92:521–26
    [Google Scholar]
  76. 76. 
    Zhou J, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL et al. 2008. Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am. J. Physiol. Endocrinol. Metab. 295:E1160–66
    [Google Scholar]
  77. 77. 
    Gao Z, Yin J, Zhang J, Ward RE, Martin RJ et al. 2009. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58:1509–17
    [Google Scholar]
  78. 78. 
    Kimura I, Inoue D, Maeda T, Hara T, Ichimura A et al. 2011. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). PNAS 108:8030–35
    [Google Scholar]
  79. 79. 
    Landsberg L. 2006. Feast or famine: the sympathetic nervous system response to nutrient intake. Cell. Mol. Neurobiol. 26:497–508
    [Google Scholar]
  80. 80. 
    Yamashita H, Maruta H, Jozuka M, Kimura R, Iwabuchi H et al. 2009. Effects of acetate on lipid metabolism in muscles and adipose tissues of type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci. Biotechnol. Biochem. 73:570–76
    [Google Scholar]
  81. 81. 
    Canfora EE, Jocken JW, Blaak EE 2015. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat. Rev. Endocrinol. 11:577–91
    [Google Scholar]
  82. 82. 
    Crouse JR, Gerson CD, DeCarli LM, Lieber CS 1968. Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man. J. Lipid Res. 9:509–12
    [Google Scholar]
  83. 83. 
    Canfora EE, van der Beek CM, Jocken JWE, Goossens GH, Holst JJ et al. 2017. Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Sci. Rep. 7:2360
    [Google Scholar]
  84. 84. 
    Jocken JWE, González Hernández MA, Hoebers NTH, van der Beek CM, Essers YPG et al. 2018. Short-chain fatty acids differentially affect intracellular lipolysis in a human white adipocyte model. Front. Endocrinol. 8:372
    [Google Scholar]
  85. 85. 
    Offermanns S. 2006. The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends Pharmacol. Sci. 27:384–90
    [Google Scholar]
  86. 86. 
    Plöger S, Stumpff F, Penner GB, Schulzke JD, Gäbel G et al. 2012. Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann. N. Y. Acad. Sci. 1258:52–59
    [Google Scholar]
  87. 87. 
    Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y et al. 2007. TLR4 enhances TGF-β signaling and hepatic fibrosis. Nat. Med. 13:1324–32
    [Google Scholar]
  88. 88. 
    Trauner M, Boyer JL. 2003. Bile salt transporters: molecular characterization, function, and regulation. Physiol. Rev. 83:633–71
    [Google Scholar]
  89. 89. 
    LaRusso NF, Hoffman NE, Korman MG, Hofmann AF, Cowen AE 1978. Determinants of fasting and postprandial serum bile acid levels in healthy man. Am. J. Dig. Dis. 23:385–91
    [Google Scholar]
  90. 90. 
    Everson GT. 1987. Steady-state kinetics of serum bile acids in healthy human subjects: single and dual isotope techniques using stable isotopes and mass spectrometry. J. Lipid Res. 28:238–52
    [Google Scholar]
  91. 91. 
    De Boever P, Wouters R, Verschaeve L, Berckmans P, Schoeters G, Verstraete W 2000. Protective effect of the bile salt hydrolase-active Lactobacillus reuteri against bile salt cytotoxicity. Appl. Microbiol. Biotechnol. 53:709–14
    [Google Scholar]
  92. 92. 
    Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM et al. 1999. Identification of a nuclear receptor for bile acids. Science 284:1362–65
    [Google Scholar]
  93. 93. 
    Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI et al. 2001. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. PNAS 98:3369–74
    [Google Scholar]
  94. 94. 
    Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H et al. 2002. Vitamin D receptor as an intestinal bile acid sensor. Science 296:1313–16
    [Google Scholar]
  95. 95. 
    Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H et al. 2003. A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278:9435–40
    [Google Scholar]
  96. 96. 
    Fujita K, Iguchi Y, Une M, Watanabe S 2017. Ursodeoxycholic acid suppresses lipogenesis in mouse liver: possible role of the decrease in β-muricholic acid, a farnesoid X receptor antagonist. Lipids 52:335–44
    [Google Scholar]
  97. 97. 
    Chiang JY. 2009. Bile acids: regulation of synthesis. J. Lipid Res. 50:1955–66
    [Google Scholar]
  98. 98. 
    Kong B, Wang L, Chiang JY, Zhang Y, Klaassen CD, Guo GL 2012. Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. Hepatology 56:1034–43
    [Google Scholar]
  99. 99. 
    Li F, Jiang C, Krausz KW, Li Y, Albert I et al. 2013. Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat. Commun. 4:2384
    [Google Scholar]
  100. 100. 
    Jiang C, Xie C, Li F, Zhang L, Nichols RG et al. 2015. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J. Clin. Investig. 125:386–402
    [Google Scholar]
  101. 101. 
    Sayin SI, Wahlström A, Felin J, Jäntti S, Marschall HU et al. 2013. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 17:225–35
    [Google Scholar]
  102. 102. 
    Parséus A, Sommer N, Sommer F, Caesar R, Molinaro A et al. 2017. Microbiota-induced obesity requires farnesoid X receptor. Gut 66:429–37
    [Google Scholar]
  103. 103. 
    Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI 2008. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3:213–23
    [Google Scholar]
  104. 104. 
    Islam KB, Fukiya S, Hagio M, Fujii N, Ishizuka S et al. 2011. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141:1773–81
    [Google Scholar]
  105. 105. 
    Inagaki T, Moschetta A, Lee YK, Peng L, Zhao G et al. 2006. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. PNAS 103:3920–25
    [Google Scholar]
  106. 106. 
    Kliewer SA, Mangelsdorf DJ. 2015. Bile acids as hormones: the FXR-FGF15/19 pathway. Dig. Dis. 33:327–31
    [Google Scholar]
  107. 107. 
    Marcelin G, Jo YH, Li X, Schwartz GJ, Zhang Y et al. 2013. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. Mol. Metab. 3:19–28
    [Google Scholar]
  108. 108. 
    Mertens KL, Kalsbeek A, Soeters MR, Eggink HM 2017. Bile acid signaling pathways from the enterohepatic circulation to the central nervous system. Front. Neurosci. 11:617
    [Google Scholar]
  109. 109. 
    Higashi T, Watanabe S, Tomaru K, Yamazaki W, Yoshizawa K et al. 2017. Unconjugated bile acids in rat brain: analytical method based on LC/ESI-MS/MS with chemical derivatization and estimation of their origin by comparison to serum levels. Steroids 125:107–13
    [Google Scholar]
  110. 110. 
    Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW et al. 2006. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439:484–89
    [Google Scholar]
  111. 111. 
    Broeders EP, Nascimento EB, Havekes B, Brans B, Roumans KH et al. 2015. The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab 22:418–26
    [Google Scholar]
  112. 112. 
    Katsuma S, Hirasawa A, Tsujimoto G 2005. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem. Biophys. Res. Commun. 329:386–90
    [Google Scholar]
  113. 113. 
    Rath S, Heidrich B, Pieper DH, Vital M 2017. Uncovering the trimethylamine-producing bacteria of the human gut microbiota. Microbiome 5:54
    [Google Scholar]
  114. 114. 
    Koeth RA, Wang Z, Levison BS, Buffa JA, Org E et al. 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19:576–85
    [Google Scholar]
  115. 115. 
    Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS et al. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63
    [Google Scholar]
  116. 116. 
    Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB et al. 2013. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368:1575–84
    [Google Scholar]
  117. 117. 
    Gao X, Liu X, Xu J, Xue C, Xue Y, Wang Y 2014. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet. J. Biosci. Bioeng. 118:476–81
    [Google Scholar]
  118. 118. 
    Chen Y-m, Liu Y, Zhou R-f, Chen X-l, Wang C et al. 2016. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults. Sci. Rep. 6:19076
    [Google Scholar]
  119. 119. 
    Blachier F, Mariotti F, Huneau JF, Tomé D 2007. Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 33:547–62
    [Google Scholar]
  120. 120. 
    Beaumont M, Andriamihaja M, Lan A, Khodorova N, Audebert M et al. 2016. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: the adaptive response. Free Radic. Biol. Med. 93:155–64
    [Google Scholar]
  121. 121. 
    Bansal T, Alaniz RC, Wood TK, Jayaraman A 2010. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. PNAS 107:228–33
    [Google Scholar]
  122. 122. 
    Whitfield-Cargile CM, Cohen ND, Chapkin RS, Weeks BR, Davidson LA et al. 2016. The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy. Gut Microbes 7:246–61
    [Google Scholar]
  123. 123. 
    Beaumont M, Neyrinck AM, Olivares M, Rodriguez J, de Rocca Serra A et al. 2018. The gut microbiota metabolite indole alleviates liver inflammation in mice. FASEB J 33:6681–93
    [Google Scholar]
  124. 124. 
    Jenne CN, Kubes P. 2013. Immune surveillance by the liver. Nat. Immunol. 14:996–1006
    [Google Scholar]
  125. 125. 
    Gregory SH, Liu CC. 2000. CD8+ T-cell-mediated response to Listeria monocytogenes taken up in the liver and replicating within hepatocytes. Immunol. Rev. 174:112–22
    [Google Scholar]
  126. 126. 
    Fox ES, Thomas P, Broitman SA 1989. Clearance of gut-derived endotoxins by the liver. Release and modification of 3H, 14C-lipopolysaccharide by isolated rat Kupffer cells. Gastroenterology 96:456–61
    [Google Scholar]
  127. 127. 
    Atif M, Warner S, Oo YH 2018. Linking the gut and liver: crosstalk between regulatory T cells and mucosa-associated invariant T cells. Hepatol. Int. 12:305–14
    [Google Scholar]
  128. 128. 
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C et al. 2007. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–72
    [Google Scholar]
  129. 129. 
    Medzhitov R. 2001. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1:135–45
    [Google Scholar]
  130. 130. 
    Martinon F, Burns K, Tschopp J 2002. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10:417–26
    [Google Scholar]
  131. 131. 
    von Meyenburg C, Hrupka BH, Arsenijevic D, Schwartz GJ, Landmann R, Langhans W 2004. Role for CD14, TLR2, and TLR4 in bacterial product-induced anorexia. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287:R298–305
    [Google Scholar]
  132. 132. 
    Denis RG, Arruda AP, Romanatto T, Milanski M, Coope A et al. 2010. TNF-α transiently induces endoplasmic reticulum stress and an incomplete unfolded protein response in the hypothalamus. Neuroscience 170:1035–44
    [Google Scholar]
  133. 133. 
    Sergeyev V, Broberger C, Hökfelt T 2001. Effect of LPS administration on the expression of POMC, NPY, galanin, CART and MCH mRNAs in the rat hypothalamus. Mol. Brain Res. 90:93–100
    [Google Scholar]
  134. 134. 
    Sartin JL, Marks DL, McMahon CD, Daniel JA, Levasseur P et al. 2008. Central role of the melanocortin-4 receptors in appetite regulation after endotoxin. J. Anim. Sci. 86:2557–67
    [Google Scholar]
  135. 135. 
    Korver DR, Roura E, Klasing KC 1998. Effect of dietary energy level and oil source on broiler performance and response to an inflammatory challenge. Poult. Sci. 77:1217–27
    [Google Scholar]
  136. 136. 
    Kushibiki S, Hodate K, Shingu H, Obara Y, Touno E et al. 2003. Metabolic and lactational responses during recombinant bovine tumor necrosis factor-α treatment in lactating cows. J. Dairy Sci. 86:819–27
    [Google Scholar]
  137. 137. 
    Campos PHRF, Merlot E, Damon M, Noblet J, Le Floc'h N 2014. High ambient temperature alleviates the inflammatory response and growth depression in pigs challenged with Escherichia coli lipopolysaccharide. Vet. J. 200:404–9
    [Google Scholar]
  138. 138. 
    Ogimoto K, Harris MK Jr, Wisse BE 2006. MyD88 is a key mediator of anorexia, but not weight loss, induced by lipopolysaccharide and interleukin-1β. Endocrinology 147:4445–53
    [Google Scholar]
  139. 139. 
    Burfeind KG, Michaelis KA, Marks DL 2016. The central role of hypothalamic inflammation in the acute illness response and cachexia. Semin. Cell Dev. Biol. 54:42–52
    [Google Scholar]
  140. 140. 
    Andus T, Bauer J, Gerok W 1991. Effects of cytokines on the liver. Hepatology 13:364–75
    [Google Scholar]
  141. 141. 
    Rosenbaum S, Ringseis R, Hillen S, Becker S, Erhardt G et al. 2012. The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation. Acta Vet. Scand. 54:59
    [Google Scholar]
  142. 142. 
    Rosenbaum S, Ringseis R, Hillen S, Becker S, Erhardt G et al. 2012. Genome-wide transcript profiling indicates induction of energy-generating pathways and an adaptive immune response in the liver of sows during lactation. Comp. Biochem. Physiol. D Genom. Proteom. 7:370–81
    [Google Scholar]
  143. 143. 
    Gessner DK, Gröne B, Couturier A, Rosenbaum S, Hillen S et al. 2015. Dietary fish oil inhibits pro-inflammatory and ER stress signalling pathways in the liver of sows during lactation. PLOS ONE 10:e0137684
    [Google Scholar]
  144. 144. 
    Gessner DK, Gröne B, Rosenbaum S, Most E, Hillen S et al. 2015. Effect of a negative energy balance induced by feed restriction on pro-inflammatory and endoplasmic reticulum stress signaling pathways in the liver and skeletal muscle of lactating sows. Arch. Anim. Nutr. 69:411–23
    [Google Scholar]
  145. 145. 
    Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH et al. 2012. Obesity is associated with hypothalamic injury in rodents and humans. J. Clin. Investig. 122:153–62
    [Google Scholar]
  146. 146. 
    Guyenet SJ, Nguyen HT, Hwang BH, Schwartz MW, Baskin DG, Thaler JP 2013. High-fat diet feeding causes rapid, non-apoptotic cleavage of caspase-3 in astrocytes. Brain Res 1512:97–105
    [Google Scholar]
  147. 147. 
    Valdearcos M, Robblee MM, Benjamin DI, Nomura DK, Xu AW, Koliwad SK 2014. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep 9:2124–38
    [Google Scholar]
  148. 148. 
    De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL et al. 2005. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146:4192–99
    [Google Scholar]
  149. 149. 
    Irani BG, Dunn-Meynell AA, Levin BE 2007. Altered hypothalamic leptin, insulin, and melanocortin binding associated with moderate-fat diet and predisposition to obesity. Endocrinology 148:310–16
    [Google Scholar]
  150. 150. 
    Könner AC, Klöckener T, Brüning JC 2009. Control of energy homeostasis by insulin and leptin: targeting the arcuate nucleus and beyond. Physiol. Behav. 97:632–38
    [Google Scholar]
  151. 151. 
    Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C et al. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS 110:9066–71
    [Google Scholar]
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