OpenLB
Open Library of Bioscience
Advanced Search
European journal of endocrinology
Aug 03, 2021;185 (3): R75-R91.

MECHANISMS IN ENDOCRINOLOGY: The gut-brain axis: regulating energy balance independent of food intake.

Ruben Nogueiras
Author Information
  1. Ruben Nogueiras: Department of Physiology, CIMUS, USC, CIBER Fisiopatolog��a Obesidad y Nutrici��n (CiberOBN), Instituto Salud Carlos III, Galician Agency of Innovation, Xunta de Galicia, Santiago de Compostela, Spain.
PMID: 34260412 DOI: 10.1530/EJE-21-0277

Abstract

Obesity is a global pandemic with a large health and economic burden worldwide. Bodyweight is regulated by the ability of the CNS, and especially the hypothalamus, to orchestrate the function of peripheral organs that play a key role in metabolism. gut hormones play a fundamental role in the regulation of energy balance, as they modulate not only feeding behavior but also energy expenditure and nutrient partitioning. This review examines the recent discoveries about hormones produced in the stomach and gut, which have been reported to regulate food intake and energy expenditure in preclinical models. Some of these hormones act on the hypothalamus to modulate thermogenesis and adiposity in a food intake-independent fashion. Finally, the association of these gut hormones to eating, energy expenditure, and weight loss after bariatric surgery in humans is discussed.

References

  1. Diabetes Care. 2013 Jul;36(7):1859-64 [PMID: 23801799]
  2. Obes Rev. 2005 Nov;6(4):297-306 [PMID: 16246215]
  3. Am J Clin Nutr. 1999 Sep;70(3 Suppl):560S-569S [PMID: 10479232]
  4. Surg Obes Relat Dis. 2021 Jul;17(7):1383-1391 [PMID: 33771461]
  5. Dig Dis. 2011;29(1):48-51 [PMID: 21691104]
  6. Nutr Metab Cardiovasc Dis. 2020 Apr 12;30(4):616-624 [PMID: 32127340]
  7. J Comp Neurol. 2005 Dec 5;493(1):63-71 [PMID: 16254991]
  8. Ann Surg. 2008 Mar;247(3):401-7 [PMID: 18376181]
  9. J Neurosci. 2009 May 6;29(18):5916-25 [PMID: 19420258]
  10. Gut. 1975 Sep;16(9):744-52 [PMID: 1104414]
  11. Gastroenterology. 2004 Mar;126(3):732-40 [PMID: 14988827]
  12. J Hypertens. 2006 Apr;24(4):621-6 [PMID: 16531786]
  13. Diabetes. 2012 Feb;61(2):292-300 [PMID: 22179810]
  14. Am J Physiol. 1999 Jun;276(6):R1569-78 [PMID: 10362733]
  15. Clin Endocrinol (Oxf). 2009 Aug;71(2):195-201 [PMID: 19178509]
  16. J Clin Endocrinol Metab. 2008 May;93(5):1971-9 [PMID: 18198223]
  17. Int J Obes Relat Metab Disord. 2004 Nov;28 Suppl 3:S2-9 [PMID: 15543214]
  18. Mol Metab. 2013 Dec 14;3(3):241-51 [PMID: 24749050]
  19. Dig Dis Sci. 1985 Dec;30(12):1145-8 [PMID: 2866074]
  20. Nature. 1999 Dec 9;402(6762):656-60 [PMID: 10604470]
  21. Proc Nutr Soc. 2007 Feb;66(1):131-55 [PMID: 17343779]
  22. EBioMedicine. 2019 Feb;40:67-76 [PMID: 30639417]
  23. J Clin Endocrinol Metab. 2002 Jan;87(1):240-4 [PMID: 11788653]
  24. Neuron. 2003 Feb 20;37(4):649-61 [PMID: 12597862]
  25. Gastroenterology. 2010 May;138(5):1997-2005 [PMID: 20117110]
  26. Physiol Rev. 2015 Apr;95(2):513-48 [PMID: 25834231]
  27. Physiol Res. 2011;60(6):941-50 [PMID: 21995902]
  28. Diabetes. 2014 Apr;63(4):1224-33 [PMID: 24296712]
  29. FASEB J. 2009 Sep;23(9):3113-20 [PMID: 19417078]
  30. Trends Mol Med. 2016 May;22(5):359-376 [PMID: 27038883]
  31. Am J Physiol Endocrinol Metab. 2012 Oct 1;303(7):E853-64 [PMID: 22829581]
  32. Mol Cell Biol. 2003 Nov;23(22):7973-81 [PMID: 14585959]
  33. Digestion. 1996 Nov-Dec;57(6):398-405 [PMID: 8913701]
  34. J Clin Invest. 1981 Oct;68(4):1106-7 [PMID: 7287903]
  35. PLoS One. 2012;7(7):e40156 [PMID: 22802954]
  36. Biochem Biophys Res Commun. 2001 Mar;281(5):1220-5 [PMID: 11243865]
  37. Metabolism. 2008 Oct;57(10):1458-64 [PMID: 18803953]
  38. Gastroenterology. 2004 Aug;127(2):546-58 [PMID: 15300587]
  39. Obes Surg. 2004 May;14(5):644-7 [PMID: 15186632]
  40. J Pharmacol Exp Ther. 2007 Jul;322(1):148-54 [PMID: 17395766]
  41. J Endocrinol Invest. 2019 Sep;42(9):1019-1027 [PMID: 30852757]
  42. Endocrinology. 2008 Feb;149(2):843-50 [PMID: 18006636]
  43. Mol Metab. 2013 Oct 17;3(1):64-72 [PMID: 24567905]
  44. Am J Clin Nutr. 1981 Feb;34(2):154-60 [PMID: 6259918]
  45. FASEB J. 1995 May;9(8):643-50 [PMID: 7768356]
  46. J Clin Endocrinol Metab. 2020 Apr 1;105(4): [PMID: 32016415]
  47. Gastroenterology. 2010 Sep;139(3):857-68 [PMID: 20546737]
  48. Diabetologia. 1986 Jan;29(1):68 [PMID: 3514345]
  49. FASEB J. 2011 Aug;25(8):2814-22 [PMID: 21543764]
  50. Peptides. 1988 Sep-Oct;9(5):993-8 [PMID: 3244567]
  51. Cell Metab. 2013 May 7;17(5):798-805 [PMID: 23663743]
  52. Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E409-15 [PMID: 21610227]
  53. Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G610-8 [PMID: 18048479]
  54. J Comp Physiol Psychol. 1973 Sep;84(3):488-95 [PMID: 4745816]
  55. Endocrinology. 2013 Sep;154(9):2992-3000 [PMID: 23782940]
  56. Obesity (Silver Spring). 2013 Dec;21(12):E660-8 [PMID: 23804517]
  57. Regul Pept. 2003 Nov 15;116(1-3):21-5 [PMID: 14599711]
  58. J Clin Endocrinol Metab. 2005 Feb;90(2):1068-71 [PMID: 15522935]
  59. J Biol Chem. 2008 Jun 27;283(26):18365-76 [PMID: 18420580]
  60. Cell. 2012 Jul 20;150(2):366-76 [PMID: 22796012]
  61. Diabetes. 2012 Nov;61(11):2753-62 [PMID: 22933116]
  62. Am J Physiol Endocrinol Metab. 2012 Jan 1;302(1):E19-31 [PMID: 21828341]
  63. Mol Metab. 2013 Oct 23;3(1):19-28 [PMID: 24567901]
  64. J Clin Endocrinol Metab. 2004 Dec;89(12):5993-7 [PMID: 15579749]
  65. J Clin Invest. 2006 Jul;116(7):1983-93 [PMID: 16767221]
  66. Surg Endosc. 2012 Aug;26(8):2231-9 [PMID: 22302537]
  67. Nat Rev Endocrinol. 2019 Feb;15(2):90-104 [PMID: 30446744]
  68. Regul Pept. 1988 May;21(1-2):151-66 [PMID: 2839871]
  69. Eur J Nutr. 2016 Mar;55(2):529-536 [PMID: 25743370]
  70. Surg Obes Relat Dis. 2013 Mar-Apr;9(2):192-201 [PMID: 23183113]
  71. Sci Transl Med. 2013 Oct 30;5(209):209ra151 [PMID: 24174327]
  72. Endocrinology. 2007 May;148(5):1954-62 [PMID: 17234710]
  73. Clin Endocrinol (Oxf). 1974 Oct;3(4):489-93 [PMID: 4430150]
  74. Nat Rev Cancer. 2004 Aug;4(8):579-91 [PMID: 15286738]
  75. Diabet Med. 2009 Mar;26(3):268-78 [PMID: 19317822]
  76. Cell Metab. 2005 Oct;2(4):217-25 [PMID: 16213224]
  77. Compr Physiol. 2019 Dec 18;10(1):99-124 [PMID: 31853954]
  78. Endocrinology. 2017 Dec 1;158(12):4139-4151 [PMID: 29040429]
  79. Diabetes Care. 2013 Sep;36(9):2810-4 [PMID: 23628619]
  80. Diabetologia. 2019 Apr;62(4):665-675 [PMID: 30683945]
  81. Diabetes. 2014 Nov;63(11):3798-804 [PMID: 24898144]
  82. Acta Anat (Basel). 1997;160(4):213-31 [PMID: 9732122]
  83. Cell Metab. 2011 Nov 2;14(5):700-6 [PMID: 22000927]
  84. Diabetes Care. 2004 Aug;27(8):1915-21 [PMID: 15277417]
  85. Am J Physiol Endocrinol Metab. 2014 Jun 1;306(11):E1248-56 [PMID: 24735885]
  86. Cell. 1990 Nov 30;63(5):941-8 [PMID: 1701694]
  87. Diabetes. 2001 Apr;50(4):707-9 [PMID: 11289032]
  88. J Clin Endocrinol Metab. 2003 Feb;88(2):853-7 [PMID: 12574224]
  89. Nature. 1996 Jan 4;379(6560):69-72 [PMID: 8538742]
  90. J Clin Invest. 2013 Nov;123(11):4799-808 [PMID: 24084738]
  91. Bioessays. 2007 Mar;29(3):248-61 [PMID: 17295284]
  92. Endocrinology. 1993 Aug;133(2):631-8 [PMID: 8102095]
  93. Endocrinology. 2003 Dec;144(12):5166-71 [PMID: 14500570]
  94. J Clin Endocrinol Metab. 2015 Mar;100(3):E396-406 [PMID: 25536209]
  95. Int J Obes (Lond). 2014 Jun;38(6):784-93 [PMID: 23999198]
  96. Lancet. 2018 Nov 17;392(10160):2180-2193 [PMID: 30293770]
  97. Metabolism. 2019 Dec;101:153997 [PMID: 31672446]
  98. Endocrinology. 1999 Jan;140(1):244-50 [PMID: 9886831]
  99. Aging Cell. 2011 Dec;10(6):996-1010 [PMID: 21895961]
  100. Gastroenterology. 1994 Jun;106(6):1451-4 [PMID: 8194689]
  101. Nat Rev Endocrinol. 2010 Apr;6(4):195-213 [PMID: 20195269]
  102. J Nutr. 2002 Apr;132(4):739-41 [PMID: 11925470]
  103. J Clin Endocrinol Metab. 2004 Feb;89(2):936-9 [PMID: 14764817]
  104. Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E614-21 [PMID: 19996386]
  105. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3242-6 [PMID: 8159732]
  106. Gastroenterology. 2006 Jan;130(1):44-54 [PMID: 16401467]
  107. Diabetes. 2005 Aug;54(8):2390-5 [PMID: 16046306]
  108. Endocrinology. 2004 Jun;145(6):2594-603 [PMID: 14976145]
  109. Annu Rev Med. 2005;56:443-58 [PMID: 15660521]
  110. Nature. 2000 Apr 6;404(6778):652-60 [PMID: 10766252]
  111. Nat Med. 2005 Jun;11(6):602-3 [PMID: 15937471]
  112. J Clin Invest. 2017 Dec 1;127(12):4217-4227 [PMID: 29202475]
  113. Endocrinology. 2008 Oct;149(10):4768-77 [PMID: 18556349]
  114. Neuroendocrinology. 1999 Nov;70(5):306-16 [PMID: 10567856]
  115. Obes Surg. 2016 May;26(5):957-65 [PMID: 26259981]
  116. N Engl J Med. 2009 Apr 9;360(15):1500-8 [PMID: 19357405]
  117. Diabetes. 2001 Aug;50(8):1714-9 [PMID: 11473029]
  118. J Clin Invest. 2005 Dec;115(12):3573-8 [PMID: 16322795]
  119. J Clin Endocrinol Metab. 2010 Aug;95(8):4072-6 [PMID: 20501690]
  120. Obes Surg. 2019 Apr;29(4):1343-1351 [PMID: 30684171]
  121. Endocrinology. 2013 Oct;154(10):3671-9 [PMID: 23832961]
  122. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8227-32 [PMID: 15148384]
  123. Nature. 2002 Aug 8;418(6898):650-4 [PMID: 12167864]
  124. Endocrinology. 2012 Aug;153(8):3613-9 [PMID: 22673227]
  125. Obesity (Silver Spring). 2013 Jul;21(7):1335-42 [PMID: 23670968]
  126. J Comp Physiol Psychol. 1975 Sep;89(7):784-90 [PMID: 1176672]
  127. Peptides. 1989 Jul-Aug;10(4):797-803 [PMID: 2587421]
  128. Science. 2003 Feb 7;299(5608):856-8 [PMID: 12574619]
  129. Ann Surg. 2010 Jul;252(1):50-6 [PMID: 20562614]
  130. Mol Metab. 2015 Mar 21;4(6):437-60 [PMID: 26042199]
  131. Obes Surg. 2011 Jan;21(1):125-30 [PMID: 21104455]
  132. JAMA. 2021 Apr 13;325(14):1414-1425 [PMID: 33755728]
  133. Ann Surg. 2009 Aug;250(2):234-41 [PMID: 19638921]
  134. Endocrinology. 2004 Jun;145(6):2585-90 [PMID: 15016721]
  135. Int J Obes (Lond). 2006 Dec;30(12):1729-36 [PMID: 16619056]
  136. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701 [PMID: 14557443]
  137. Cell Metab. 2011 Jun 8;13(6):729-38 [PMID: 21641554]
  138. Gastroenterology. 2007 May;132(6):2158-68 [PMID: 17498509]
  139. Mol Metab. 2019 Dec;30:72-130 [PMID: 31767182]
  140. Am J Physiol Endocrinol Metab. 2007 Apr;292(4):E1062-8 [PMID: 17148749]
  141. Endocrinology. 2013 Jan;154(1):9-15 [PMID: 23183168]
  142. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52 [PMID: 17473055]
  143. Lancet. 2009 Nov 7;374(9701):1606-16 [PMID: 19853906]
  144. Obes Surg. 2017 Mar;27(3):703-708 [PMID: 27565666]
  145. Cell Metab. 2013 Jul 2;18(1):86-98 [PMID: 23823479]
  146. J Clin Invest. 2011 Sep;121(9):3578-88 [PMID: 21865642]
  147. J Clin Endocrinol Metab. 2004 Mar;89(3):1319-24 [PMID: 15001628]
  148. Trends Mol Med. 2008 Dec;14(12):539-49 [PMID: 18977694]
  149. Cell. 2004 Jan 23;116(2):337-50 [PMID: 14744442]
  150. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):947-51 [PMID: 1346555]
  151. Annu Rev Physiol. 1997;59:257-71 [PMID: 9074764]
  152. Nat Med. 2000 Jul;6(7):802-7 [PMID: 10888930]
  153. Eur J Endocrinol. 2001 Nov;145(5):669-73 [PMID: 11720888]
  154. Circulation. 2001 Oct 23;104(17):2034-8 [PMID: 11673342]
  155. Int J Obes Relat Metab Disord. 2003 Apr;27(4):450-6 [PMID: 12664078]
  156. Nat Rev Endocrinol. 2011 Nov 15;8(1):5-6 [PMID: 22083088]
  157. Nat Chem Biol. 2009 Oct;5(10):749-57 [PMID: 19597507]
  158. Can J Biochem. 1971 Aug;49(8):867-72 [PMID: 5120249]
  159. J Clin Invest. 2006 Jul;116(7):1761-6 [PMID: 16823473]
  160. Trends Mol Med. 2011 Aug;17(8):405-11 [PMID: 21602104]
  161. Nat Med. 2002 Jul;8(7):738-42 [PMID: 12068290]
  162. J Clin Endocrinol Metab. 2001 Dec;86(12):5830-7 [PMID: 11739447]
  163. Endocrinology. 2007 Aug;148(8):3998-4006 [PMID: 17495002]
  164. Nature. 2006 Sep 21;443(7109):289-95 [PMID: 16988703]
  165. J Clin Endocrinol Metab. 1982 Aug;55(2):329-36 [PMID: 7045154]
  166. Trends Endocrinol Metab. 2016 Jan;27(1):54-63 [PMID: 26542050]
  167. Biochem Biophys Res Commun. 2000 Dec 29;279(3):909-13 [PMID: 11162448]
  168. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4679-84 [PMID: 15070777]
  169. Nature. 2000 Oct 19;407(6806):908-13 [PMID: 11057670]
  170. Genes Dev. 2013 Feb 1;27(3):234-50 [PMID: 23388824]
  171. N Engl J Med. 2009 Apr 9;360(15):1509-17 [PMID: 19357406]
  172. Diabetes. 2014 Jul;63(7):2332-43 [PMID: 24584548]
  173. Endocrinology. 2001 Oct;142(10):4244-50 [PMID: 11564680]
  174. Cell Metab. 2005 Jan;1(1):15-25 [PMID: 16054041]
  175. Surg Obes Relat Dis. 2006 Sep-Oct;2(5):538-48 [PMID: 17015210]
  176. Obesity (Silver Spring). 2015 Mar;23(3):591-601 [PMID: 25707380]
  177. Int J Pept. 2010;2010: [PMID: 20798765]
  178. Biochem Biophys Res Commun. 2003 Nov 28;311(4):915-9 [PMID: 14623268]
  179. Acta Endocrinol (Copenh). 1986 Jun;112(2):224-9 [PMID: 3526784]
  180. J Clin Endocrinol Metab. 1999 Jul;84(7):2513-7 [PMID: 10404829]
  181. Endocrinology. 2002 Sep;143(9):3341-50 [PMID: 12193546]
  182. Trends Pharmacol Sci. 2018 Aug;39(8):685-694 [PMID: 30037389]
  183. Endocrinology. 1987 Sep;121(3):1076-82 [PMID: 3040376]
  184. Obes Rev. 2020 Aug;21(8):e13038 [PMID: 32329176]
  185. Physiol Behav. 1988;44(4-5):645-9 [PMID: 3237850]
  186. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2364-2372 [PMID: 28379519]
  187. Diabetes. 2016 Feb;65(2):421-32 [PMID: 26566631]
  188. N Engl J Med. 2014 Apr 3;370(14):1363-4 [PMID: 24693908]
  189. Int J Obes Relat Metab Disord. 2004 Aug;28(8):963-71 [PMID: 15197409]
  190. Ann Surg. 1990 Jun;211(6):763-70; discussion 770-1 [PMID: 2192696]
  191. Annu Rev Neurosci. 2007;30:367-98 [PMID: 17506645]
  192. FEBS Lett. 1995 Jul 24;368(3):488-90 [PMID: 7635205]
  193. Diabetes. 2014 Oct;63(10):3346-58 [PMID: 24917578]
  194. Nat Metab. 2019 Jun;1(6):588-594 [PMID: 32694803]
  195. Trends Neurosci. 2017 Mar;40(3):167-180 [PMID: 28108113]
  196. Int J Obes (Lond). 2008 Sep;32 Suppl 4:S55-9 [PMID: 18719600]
  197. J Clin Endocrinol Metab. 1983 Sep;57(3):488-95 [PMID: 6874888]
  198. Endocrinology. 2009 Oct;150(10):4562-74 [PMID: 19608647]
  199. Peptides. 2018 Feb;100:190-201 [PMID: 29412819]
  200. Steroids. 2012 Mar 10;77(4):323-31 [PMID: 22178258]
  201. Am J Physiol. 1994 May;266(5 Pt 1):G887-91 [PMID: 8203533]
  202. N Engl J Med. 2009 Apr 9;360(15):1518-25 [PMID: 19357407]

MeSH Term

Adipose Tissue
Animals
Brain
Eating
Energy Metabolism
Gastric Mucosa
Gastrointestinal Hormones
Gastrointestinal Tract
Humans
Hypothalamus
Obesity

Chemicals

Gastrointestinal Hormones
Journal Article Review
Article has an altmetric score of 3

Word Cloud

Created with Highcharts 10.0.0energyhormonesexpenditurefoodhypothalamusplayrolebalancemodulategutintakeObesityglobalpandemiclargehealtheconomicburdenworldwideBodyweightregulatedabilityCNSespeciallyorchestratefunctionperipheralorganskeymetabolismGutfundamentalregulationfeedingbehavioralsonutrientpartitioningreviewexaminesrecentdiscoveriesproducedstomachreportedregulatepreclinicalmodelsactthermogenesisadiposityintake-independentfashionFinallyassociationeatingweightlossbariatricsurgeryhumansdiscussedMECHANISMSINENDOCRINOLOGY:gut-brainaxis:regulatingindependent

Similar Articles

Cited By