Biomechanics and Modeling in Mechanobiology

, Volume 18, Issue 6, pp 1915–1926 | Cite as

Refeeding reverses fasting-induced remodeling of afferent nerve activity in rat small intestine

  • Lingxia Bao
  • Jingbo Zhao
  • Donghua Liao
  • Guixue Wang
  • Hans GregersenEmail author
Original Paper


Intestinal afferents play an important role in coordinating intestinal motor control. Fasting induces morpho-mechanical intestinal remodeling. This study aimed to characterize the effect of fasting and refeeding on mechanosensitivity in mesenteric afferent nerves in isolated Sprague–Dawley rat jejunum. A control group fed ad libitum, a group fasted for 7 days and a group refed 7 days after 7 days fasting were studied. Jejunal segments were used for electrophysiological, histomorphological and mechanical studies. Mesenteric afferent nerve firing was recorded during a ramp distension up to 40 mmHg luminal pressure. Multiunit afferent recordings were separated into low threshold and wide-dynamic-range single-unit activity. Intestinal deformation (strain), bowel distension load (stress) and firing frequency of mesenteric afferent nerve bundles [spike rate increase ratio (SRIR)] were compared among groups. Fasting induced intestinal histomorphometric remodeling, which was reversed by refeeding. The firing frequency increased with distension in all groups. SRIR was largest in the fasting group (P < 0.05). Compared to the control group, fasting increased afferent activity in whole nerve bundles and wide-dynamic-range units at high degrees of distensions (P < 0.05 at pressure 40 mmHg; P < 0.05 at strain 1.2; P < 0.01 at stress 8 kPa). Refeeding reversed the fasting-induced afferent hypersensitivity and the shift between receptor subtypes. In conclusion, refeeding reversed fasting-induced remodeling.


Fasting Ramp distension Mesenteric afferents Mechanosensitivity Remodeling 



The studies were financially supported by grants from Chongqing Science and Technology Commission (cstc2013kjrc-ljrccj10003), National “111 Plan” Base (B06023) and Danish Karen Elise Jensen Foundation (Grant No. 903959).

Author’s contributions

All authors participated in the study design and contributed to the manuscript. LB conducted the animal experiments and analyzed the data with JZ and DL. All authors contributed to the interpretation of the data. LB drafted the manuscript that was revised by the coauthors. HG obtained the funding. All authors read and approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Bertile F, Oudart H, Criscuolo F, Maho YL, Raclot T (2003) Hypothalamic gene expression in long-term fasted rats: relationship with body fat. Biochem Biophys Res Commun 303(4):1106–1113. CrossRefGoogle Scholar
  2. Booth CE, Shaw J, Hicks GA, Kirkup AJ, Winchester W, Grundy D (2008) Influence of the pattern of jejunal distension on mesenteric afferent sensitivity in the anaesthetized rat. Neurogastroenterol Motil 20(2):149–158. CrossRefGoogle Scholar
  3. Bray GA (2000) Treatment and secondary prevention of obesity. Nutrition 16(5):384–385. CrossRefGoogle Scholar
  4. Broberger C, Holmberg K, Shi TJ, Dockray G, Hokfelt T (2001) Expression and regulation of cholecystokinin and cholecystokinin receptors in rat nodose and dorsal root ganglia. Brain Res 903(1–2):128–140. CrossRefGoogle Scholar
  5. Burdyga G, Varro A, Dimaline R, Thompson DG, Dockray GJ (2006) Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance. Am J Physiol Gastrointest Liver Physiol 290(6):1289–1297. CrossRefGoogle Scholar
  6. Burdyga G, de Lartigue G, Raybould HE, Morris R, Dimaline R, Varro A, Thompson DG, Dockray GJ (2008) Cholecystokinin regulates expression of Y2 receptors in vagal afferent neurons serving the stomach. J Neurosci 28(45):11583–11592. CrossRefGoogle Scholar
  7. Chen PM, Zhao JB, Nielsen VH, Clausen T, Gregersen H (2009) Intestinal remodelling in mink fed with reduced protein content. J Biomech 42(4):443–448. CrossRefGoogle Scholar
  8. Cherel Y, Le Maho Y (1991) Refeeding after the late increase in nitrogen excretion during prolonged fasting in the rat. Physiol Behav 50(2):345–349. CrossRefGoogle Scholar
  9. Date Y, Toshinai K, Koda S, Miyazato M, Shimbara T, Tsuruta T, Niijima A, Kangawa K, Nakazato M (2005) Peripheral interaction of ghrelin with cholecystokinin on feeding regulation. Endocrinology 146(8):3518–3525. CrossRefGoogle Scholar
  10. Dockray G (2004) Gut endocrine secretions and their relevance to satiety. Curr Opin Pharmacol 4(6):557–560. CrossRefGoogle Scholar
  11. Dou YL, Gregersen S, Zhao JB, Zhuang F, Gregersen H (2001) Effect of re-feeding after starvation on biomechanical properties in rat small intestine. Med Eng Phys 23(8):557–566. CrossRefGoogle Scholar
  12. Dou YL, Gregersen S, Zhao JB, Zhuang F, Gregersen H (2002) Morphometric and biomechanical intestinal remodeling induced by fasting in rats. Dig Dis Sci 47(5):1158–1168. CrossRefGoogle Scholar
  13. Elfazaa S, Somody L, Gharbi N, Kamoun A, Gharib C, Gauquelin-Koch G (1999) Effects of acute and chronic starvation on central and peripheral noradrenaline turnover, blood pressure and heart rate in the rat. Exp Physiol 84(2):357–368CrossRefGoogle Scholar
  14. Geracioti TD Jr, Liddle RA (1988) Impaired cholecystokinin secretion in bulimia nervosa. N Engl J Med 319(11):683–688. CrossRefGoogle Scholar
  15. Gomes OA, Castelucci P, de Vasconcellos Fontes RB, Liberti EA (2006) Effects of pre- and postnatal protein deprivation and postnatal refeeding on myenteric neurons of the rat small intestine: a quantitative morphological study. Auton Neurosci 126–127:277–284. CrossRefGoogle Scholar
  16. Gomez R, Navarro M, Ferrer B, Trigo JM, Bilbao A, Del Arco I, Cippitelli A, Nava F, Piomelli D, Rodriguez de Fonseca F (2002) A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 22(21):9612–9617. CrossRefGoogle Scholar
  17. Greggio FM, Fontes RB, Maifrino LB, Castelucci P, de Souza RR, Liberti EA (2010) Effects of perinatal protein deprivation and recovery on esophageal myenteric plexus. World J Gastroenterol 16(5):563–570CrossRefGoogle Scholar
  18. Kentish S, Li H, Philp LK, O’Donnell TA, Isaacs NJ, Young RL, Wittert GA, Blackshaw LA, Page AJ (2002) Diet-induced adaptation of vagal afferent function. J Physiol 590(1):209–221. CrossRefGoogle Scholar
  19. Kentish SJ, O’Donnell TA, Wittert GA, Page AJ (2014) Diet-dependent modulation of gastro-oesphageal vagal afferent mechanosensitivity by endogenous nitric oxide. J Physiol 592(15):3287–3301. CrossRefGoogle Scholar
  20. Konturek SJ, Konturek JW, Pawlik T, Brzozowski T (2004) Brain-gut axis and its role in the control of food intake. J Physiol Pharmacol 55(1 Pt 2):137–154Google Scholar
  21. Langley K (1994) The neuroendocrine concept today. Ann N Y Acad Sci 733:1–17. CrossRefGoogle Scholar
  22. Liberti EA, Fontes RB, Fuggi VM, Maifrino LB, Souza RR (2007) Effects of combined pre- and post-natal protein deprivation on the myenteric plexus of the esophagus of weanling rats: a histochemical, quantitative and ultrastructural study. World J Gastroenterol 13(26):3598–3604CrossRefGoogle Scholar
  23. Liu Y, Zhao JB, Liao DH, Bao LX, Gregersen H (2017a) Low-residue diet fed to rabbits induces histomorphological and biomechanical remodeling of small intestine. Neurogastroenterol Motil. CrossRefGoogle Scholar
  24. Liu Y, Zhao JB, Liao DH, Wang GX, Gregersen H (2017b) Intestinal mechanomorphological remodeling induced by long-term low-fiber diet in rabbits. Ann Biomed Eng 45(12):2867–2878CrossRefGoogle Scholar
  25. Moriya A, Fukuwatari T, Sano M, Shibata K (2012) Different variations of tissue B-group vitamin concentrations in short- and long-term starved rats. Br J Nutr 107(1):52–60. CrossRefGoogle Scholar
  26. Page AJ, Kentish SJ (2017) Plasticity of gastrointestinal vagal afferent satiety signals. Neurogastroenterol Motil. CrossRefGoogle Scholar
  27. Peters JH, Simasko SM, Ritter RC (2006) Modulation of vagal afferent excitation and reduction of food intake by leptin and cholecystokinin. Physiol Behav 89(4):477–485. CrossRefGoogle Scholar
  28. Phillips RJ, Baronowsky EA, Powley TL (2003) Long-term regeneration of abdominal vagus: efferents fail while afferents succeed. J Comp Neurol 455(2):222–237. CrossRefGoogle Scholar
  29. Quian QR, Nadasdy Z, Ben-Shaul Y (2004) Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering. Neural Comput 16(8):1661–1687. CrossRefzbMATHGoogle Scholar
  30. Rixon RH, Stevenson JAF (1957) Factors influencing survival of rats in fasting metabolic rate and body weight loss. Am J Physiol 188(2):332–336. CrossRefGoogle Scholar
  31. Rogers RC, McTigue DM, Hermann GE (1996) Vagal control of digestion: modulation by central neural and peripheral endocrine factors. Neurosci Biobehav Rev 20(1):57–66. CrossRefGoogle Scholar
  32. Wang H, Chen B, Chow SC (2003) Sample size determination based on rank tests in clinical trials. J Biopharm Stat 13(4):735–751. CrossRefzbMATHGoogle Scholar
  33. Yang J, Zhao JB, Jiang W, Nakaguchi T, Kunwald P, Grundy D, Gregersen H (2012) Neurogenic adaptation contributes to the afferent response to mechanical stimulation. Am J Physiol Gastrointest Liver Physiol 302(9):1025–1034. CrossRefGoogle Scholar
  34. Yang J, Zhao JB, Chen PM, Toshiya N, Grundy D, Gregersen H (2016) Interdependency between mechanical parameters and afferent nerve discharge in hypertrophic intestine of rats. Am J Physiol Gastrointest Liver Physiol 310(6):376–386. CrossRefGoogle Scholar
  35. Zhang X, Ji RR, Arvidsson J, Lundberg JM, Bartfai T, Bedecs K, Hokfelt T (1996) Expression of peptides, nitric oxide synthase and NPY receptor in trigeminal and nodose ganglia after nerve lesions. Exp Brain Res 111(3):393–404CrossRefGoogle Scholar
  36. Zhang X, Shi T, Holmberg K, Landry M, Huang W, Xiao H, Ju G, Hokfelt T (1997) Expression and regulation of the neuropeptide YY2 receptor in sensory and autonomic ganglia. Proc Natl Acad Sci USA 94(2):729–734CrossRefGoogle Scholar
  37. Zhao JB, Yang J, Gregersen H (2003) Biomechanical and morphometric intestinal remodelling during experimental diabetes in rats. Diabetologia 46(12):1688–1697. CrossRefGoogle Scholar
  38. Zhao JB, Yang J, Liao DH, Gregersen H (2017) Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine. Clin Exp Gastroenterol 10:303–314. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.GIOME and the Key Laboratory for Biorheological Science and Technology of Ministry of Education; State and Local Joint Engineering Laboratory for Vascular Implants, College of BioengineeringChongqing UniversityChongqingChina
  2. 2.Giome Academia, Department of Clinical MedicineAarhus UniversityAarhus NDenmark
  3. 3.GIOME, Department of SurgeryPrince of Wales Hospital, The Chinese University of Hong KongShatinHong Kong, SAR

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