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Mazzoccoli G, De Cosmo S, Mazza T. The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis. Front Physiol. 2018;9:193doi: 10.3389/fphys.2018.00193.
Mazzoccoli, G., De Cosmo, S., & Mazza, T. (2018). The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis. Frontiers in physiology, 9193. https://doi.org/10.3389/fphys.2018.00193
Mazzoccoli, Gianluigi, et al. "The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis." Frontiers in physiology vol. 9 (2018): 193. doi: https://doi.org/10.3389/fphys.2018.00193
Mazzoccoli G, De Cosmo S, Mazza T. The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis. Front Physiol. 2018 Mar 15;9:193. doi: 10.3389/fphys.2018.00193. eCollection 2018. PMID: 29662454; PMCID: PMC5890189.
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Front Physiol. 2018 Mar 15;9:193. doi: 10.3389/fphys.2018.00193. eCollection 2018.

The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis.

Frontiers in physiology

Gianluigi Mazzoccoli, Salvatore De Cosmo, Tommaso Mazza

Affiliations

  1. Division of Internal Medicine and Chronobiology Unit, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
  2. Bioinformatics Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.

PMID: 29662454 PMCID: PMC5890189 DOI: 10.3389/fphys.2018.00193

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic pathology in the Western world and may evolve into steatohepatitis (NASH), increasing the risk of cirrhosis, portal hypertension and hepatocellular carcinoma. NAFLD derives from the accumulation of hepatic fat due to discrepant free fatty acid metabolism. Other factors contributing to this are deranged nutrients and bile acids fluxes as well as alterations in nuclear receptors, hormones, and intermediary metabolites, which impact on signaling pathways involved in metabolism and inflammation. Autophagy and host gut-microbiota interplay are also relevant to NAFLD pathogenesis. Notably, liver metabolic pathways and bile acid synthesis as well as autophagic and immune/inflammatory processes all show circadian patterns driven by the biological clock. Gut microbiota impacts on the biological clock, at the same time as the appropriate timing of metabolic fluxes, hormone secretion, bile acid turnover, autophagy and inflammation with behavioural cycles of fasting/feeding and sleeping/waking is required to circumvent hepatosteatosis, indicating significant interactions of the gut and circadian processes in NAFLD pathophysiology. Several time-related factors and processes interplay in NAFLD development, with the biological clock proposed to act as a network level hub. Deranged physiological rhythms (chronodisruption) may also play a role in liver steatosis pathogenesis. The current article reviews how the circadian clock circuitry intimately interacts with several mechanisms involved in the onset of hepatosteatosis and its progression to NASH, thereby contributing to the global NAFLD epidemic.

Keywords: NAFLD; chronodisruption; circadian; clock gene; metabolism; rhythm

References

  1. Diabetologia. 2011 Jan;54(1):120-4 - PubMed
  2. Chronobiol Int. 2013 Aug;30(7):870-88 - PubMed
  3. PLoS Med. 2014 Jul 22;11(7):e1001680 - PubMed
  4. Nat Rev Mol Cell Biol. 2015 Aug;16(8):461-72 - PubMed
  5. Nat Rev Gastroenterol Hepatol. 2013 Nov;10 (11):686-90 - PubMed
  6. Diabetes Care. 2010 Oct;33(10):2156-63 - PubMed
  7. Cell Metab. 2012 Jun 6;15(6):848-60 - PubMed
  8. Biochim Biophys Acta. 2016 Apr;1863(4):596-606 - PubMed
  9. PLoS Med. 2011 Dec;8(12):e1001141 - PubMed
  10. EMBO J. 2011 Sep 06;30(22):4642-51 - PubMed
  11. J Gastroenterol Hepatol. 2013 Dec;28 Suppl 4:59-63 - PubMed
  12. Nat Med. 2013 Sep;19(9):1147-52 - PubMed
  13. Diabetes Obes Metab. 2016 Apr;18(4):355-65 - PubMed
  14. Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3339-44 - PubMed
  15. Nature. 2012 Feb 01;482(7384):179-85 - PubMed
  16. Sci Transl Med. 2012 Apr 11;4(129):129ra43 - PubMed
  17. J Hepatol. 2013 May;58(5):993-9 - PubMed
  18. Nat Rev Genet. 2017 Mar;18(3):164-179 - PubMed
  19. Gastroenterology. 2015 Mar;148(3):547-55 - PubMed
  20. Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):E6579-88 - PubMed
  21. Hepatology. 2015 Feb;61(2):497-505 - PubMed
  22. Nat Med. 2013 Jan;19(1):83-92 - PubMed
  23. Nature. 2011 Dec 14;480(7378):552-6 - PubMed
  24. Mol Cell Endocrinol. 2015 Dec 5;417:131-40 - PubMed
  25. Cell Metab. 2017 Sep 5;26(3):523-538.e5 - PubMed
  26. Cell Metab. 2017 May 2;25(5):1054-1062.e5 - PubMed
  27. Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):E1673-82 - PubMed
  28. Pediatr Res. 2015 Jan;77(1-2):236-44 - PubMed
  29. Nat Rev Gastroenterol Hepatol. 2016 Apr;13(4):217-26 - PubMed
  30. Cancer Cell. 2016 Dec 12;30(6):909-924 - PubMed
  31. Toxicol Appl Pharmacol. 2014 Jul 1;278(1):65-71 - PubMed
  32. Nat Rev Endocrinol. 2017 Aug;13(8):445-457 - PubMed
  33. Front Neuroendocrinol. 2015 Jul;38:50-64 - PubMed
  34. Am J Clin Nutr. 2014 Feb;99(2):392-9 - PubMed
  35. Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:231-252 - PubMed
  36. Annu Rev Nutr. 2015 ;35:215-37 - PubMed
  37. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16219-24 - PubMed
  38. PLoS One. 2014 May 16;9(5):e97302 - PubMed
  39. Diabetes. 2003 Jul;52(7):1709-15 - PubMed
  40. Int J Obes (Lond). 2010 Nov;34(11):1589-98 - PubMed
  41. Hepatology. 2016 Apr;63(4):1396-7 - PubMed
  42. Cell. 2016 Dec 1;167(6):1495-1510.e12 - PubMed
  43. Am J Clin Nutr. 2017 Nov;106(5):1213-1219 - PubMed
  44. Sleep. 2014 Oct 01;37(10):1715-9 - PubMed
  45. Science. 2005 May 13;308(5724):1043-5 - PubMed
  46. Front Endocrinol (Lausanne). 2016 Jan 19;6:193 - PubMed
  47. Metabolism. 2015 Dec;64(12 ):1650-7 - PubMed
  48. Gastroenterology. 2014 Mar;146(3):726-35 - PubMed
  49. Nature. 2014 Dec 4;516(7529):108-11 - PubMed
  50. Nature. 2014 Dec 4;516(7529):112-5 - PubMed
  51. Cell Metab. 2010 Jan;11(1):47-57 - PubMed
  52. Biochim Biophys Acta. 2016 Aug;1857(8):1344-1351 - PubMed
  53. Cell Metab. 2016 Jun 14;23 (6):1067-1077 - PubMed
  54. Cell Metab. 2013 Feb 5;17(2):303-10 - PubMed
  55. Nature. 2012 Mar 29;485(7396):123-7 - PubMed
  56. Liver Int. 2014 Sep;34(8):1133-52 - PubMed
  57. Cell Metab. 2016 Sep 13;24(3):434-446 - PubMed
  58. Diabetes. 2016 Jun;65(6):1741-51 - PubMed
  59. J Biol Chem. 2016 Jul 15;291(29):15378-87 - PubMed
  60. Gastroenterology. 2008 Aug;135(2):689-98 - PubMed
  61. Nat Rev Endocrinol. 2017 Jan;13(1):36-49 - PubMed
  62. Cell Metab. 2016 Jun 14;23 (6):1048-1059 - PubMed
  63. J Hepatol. 2014 Nov;61(5):1126-34 - PubMed
  64. Trends Endocrinol Metab. 2013 Jan;24(1):4-12 - PubMed
  65. Cell Metab. 2017 Jul 5;26(1):267-277.e2 - PubMed
  66. Diabetologia. 2013 Mar;56(3):497-507 - PubMed
  67. J Gastroenterol Hepatol. 2013 Dec;28 Suppl 4:81-7 - PubMed
  68. Future Med Chem. 2011 Apr;3(5):623-38 - PubMed
  69. PLoS One. 2011;6(9):e25231 - PubMed
  70. Cell. 2014 Oct 23;159(3):514-29 - PubMed
  71. Nat Cell Biol. 2011 Feb;13(2):132-41 - PubMed
  72. Clin Nutr. 2017 Apr 10;: - PubMed
  73. Pharmacol Res. 2009 Sep;60(3):151-9 - PubMed
  74. Biochem Biophys Res Commun. 2015 Apr 3;459(2):300-5 - PubMed
  75. Science. 2011 Mar 11;331(6022):1315-9 - PubMed
  76. Cell Metab. 2014 Dec 2;20(6):991-1005 - PubMed
  77. Nat Rev Gastroenterol Hepatol. 2012 May 08;9(7):372-81 - PubMed
  78. Cell Metab. 2017 Oct 3;26(4):672-685.e4 - PubMed
  79. Biochem Pharmacol. 2013 May 15;85(10 ):1405-16 - PubMed
  80. Chronobiol Int. 2012 Apr;29(3):227-51 - PubMed
  81. J Biol Chem. 2002 Nov 15;277(46):44244-51 - PubMed
  82. Cell Metab. 2015 Oct 6;22(4):709-20 - PubMed
  83. Mol Endocrinol. 2006 Aug;20(8):1715-27 - PubMed
  84. Nat Med. 2012 Dec;18(12):1768-77 - PubMed
  85. Genes Cells. 2010 Feb;15(2):111-21 - PubMed
  86. Physiol Rev. 2013 Jan;93(1):107-35 - PubMed
  87. Diabetes. 2014 Nov;63(11):3674-85 - PubMed
  88. Genes Dev. 2012 Apr 1;26(7):657-67 - PubMed
  89. Mol Cell Biol. 2010 Jun;30(12):3059-70 - PubMed
  90. Cell. 2013 May 9;153(4):812-27 - PubMed
  91. Metabolism. 2016 May;65(5):714-27 - PubMed
  92. Curr Top Dev Biol. 2014;110:339-72 - PubMed
  93. Nature. 2009 Apr 23;458(7241):1056-60 - PubMed
  94. Cell. 2010 Sep 17;142(6):943-53 - PubMed
  95. Gut. 2017 Jan;66(1):180-190 - PubMed
  96. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16647-53 - PubMed
  97. Trends Endocrinol Metab. 2012 Dec;23(12):594-601 - PubMed
  98. Science. 2015 Nov 6;350(6261):aac4250 - PubMed
  99. Trends Mol Med. 2016 Jan;22(1):68-81 - PubMed
  100. Sci Rep. 2016 Sep 16;6:33386 - PubMed
  101. Hepatology. 2015 Feb;61(2):486-96 - PubMed
  102. Gut. 2016 Jul;65(7):1202-14 - PubMed
  103. Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5541-6 - PubMed
  104. Trends Endocrinol Metab. 2012 Jul;23(7):319-25 - PubMed
  105. Curr Opin Gastroenterol. 2016 Jan;32(1):7-11 - PubMed
  106. Nat Cell Biol. 2017 Feb;19(2):94-105 - PubMed
  107. Cell Metab. 2017 Jan 10;25(1):118-127 - PubMed
  108. Cell Metab. 2008 Dec;8(6):482-91 - PubMed
  109. Cell Metab. 2016 Apr 12;23 (4):610-21 - PubMed
  110. Cell Death Dis. 2014 Apr 17;5:e1179 - PubMed
  111. Aging (Albany NY). 2014 Jan;6(1):48-57 - PubMed
  112. Gastroenterology. 2016 Mar;150(3):574-80 - PubMed
  113. Clin Gastroenterol Hepatol. 2016 Feb;14 (2):301-8.e1-2 - PubMed
  114. Nat Med. 2010 Oct;16(10):1152-6 - PubMed
  115. Prog Mol Biol Transl Sci. 2013;119:1-28 - PubMed
  116. Cell Host Microbe. 2015 May 13;17(5):681-9 - PubMed
  117. J Atheroscler Thromb. 2005;12(3):169-74 - PubMed
  118. Diabetologia. 2016 Apr;59(4):734-43 - PubMed
  119. PLoS Biol. 2004 Nov;2(11):e377 - PubMed
  120. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2625-9 - PubMed
  121. Gastroenterology. 2014 Feb;146(2):539-49.e7 - PubMed
  122. Trends Endocrinol Metab. 2017 Jul;28(7):497-505 - PubMed
  123. Aliment Pharmacol Ther. 2012 Nov;36(9):815-23 - PubMed
  124. Nature. 2010 Jul 29;466(7306):627-31 - PubMed
  125. J Biol Chem. 2015 Jan 23;290(4):2189-97 - PubMed
  126. Hepatology. 2015 Jun;61(6):1908-19 - PubMed
  127. Front Endocrinol (Lausanne). 2017 Feb 13;8:24 - PubMed
  128. Hepatology. 2012 Jun;55(6):2005-23 - PubMed
  129. Science. 2013 Nov 1;342(6158):1243417 - PubMed
  130. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15172-7 - PubMed

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