Digestive Diseases and Sciences

, Volume 52, Issue 10, pp 2695–2702 | Cite as

Pilot Studies to Demonstrate That Intestinal Mucosal Afferent Nerves Are Functionally Linked to Visceral Adipose Tissue

  • Felix W. Leung
  • Vay Liang W. Go
  • Oscar U. Scremin
  • Andre Obenaus
  • Michael L. Tuck
  • Michael S. Golub
  • Peter Eggena
  • Joseph W. Leung
Original Article


Dietary capsaicin reduces rodent visceral fat weight. We tested the hypothesis that intact intestinal mucosal afferent nerve function is necessary for fat deposition in visceral adipose tissue sites. Rats were treated daily for 2 weeks with intragastric (chronic treatment) vehicle or capsaicin. Superior mesenteric artery blood flow and mesenteric and inguinal fat blood flow were measured before and after capsaicin was administered into the duodenum (acute treatment). Fat from all sites was dissected and weighed. Chronic capsaicin significantly attenuated acute capsaicin-induced mesenteric hyperemia but did not abolish the reflex wiping of the eye exposed to capsaicin, indicating that functional ablation was limited to the intestinal mucosal afferent nerves. The associated vasoconstriction in adipose tissue was inhibited at the visceral (mesenteric) site and maintained but attenuated at the subcutaneous (inguinal) site. The onset of vasoconstriction was instantaneous, indicating a reflex mechanism. There was a redistribution of fat from visceral to subcutaneous sites, reflected by a decrease and an increase in the percentage of body fat in the visceral and subcutaneous sites, respectively. These pilot studies reveal for the first time that normal intestinal mucosal afferent nerve function is necessary for the physiologic accumulation of fat in visceral adipose tissue sites.


Capsaicin Capsaicin-sensitive afferent nerves Pulse Doppler flowmetry Hydrogen gas clearance Laser Doppler flowmetry Adipose tissue blood flow Mesenteric artery blood flow 



This work was supported in part by VA Medical Research Funds (F.W.L.), Mr. C. W. Law Research Funds (J.W.L.), and NCI 1 P01 CA42710, UCLA Clinical Nutrition Research Unit (V.L.W.G.)


  1. 1.
    Melnyk A, Himms-Hagen J (1995) Resistance to aging-associated obesity in capsaicin-desensitized rats one year after treatment. Obesity Res 3:337–344Google Scholar
  2. 2.
    Gram DX, Hansen AJ, Wilken M, Elm T, Svendsen O, Carr RD, Ahren B, Brand CL (2005) Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats. Eur J Endocrinol 153(6):963–969PubMedCrossRefGoogle Scholar
  3. 3.
    Kawada T, Hagihara K, Iwai K (1986) Effects of capsaicin on lipid metabolism in rats fed a high fat diet. J Nutr 116:1272–1278PubMedGoogle Scholar
  4. 4.
    Ohnuki K, Haramizu S, Oki K, Watanabe T, Yazawa S, Fushiki T (2001) Administration of capsiate, a non-pungent capsaicin analog, promotes energy metabolism and suppresses body fat accumulation in mice. Biosci Biotechnol Biochem 65(12):2735–2740PubMedCrossRefGoogle Scholar
  5. 5.
    Leung FW (1993) Primary sensory nerves mediate in part the protective mesenteric hyperemia after intraduodenal acidification in rats. Gastroenterology 105:1737–1745PubMedGoogle Scholar
  6. 6.
    Leung FW (1992) Modulation of autoregulatory escape by capsaicin-sensitive afferent nerves in rat stomach. Am J Physiol 262:H562–H567PubMedGoogle Scholar
  7. 7.
    Leung FW (1992) Role of capsaicin-sensitive afferent nerves in mucosal injury and injury-induced hyperemia in rat colon. Am J Physiol 262:G332–G337PubMedGoogle Scholar
  8. 8.
    Seno K, Lam K, Leung JWC, Leung FW (1996) Primary afferent nerves mediate in part beta-adrenoceptor stimulation-induced mesenteric hyperemia in rats. Life Sci 59:1203–1209PubMedCrossRefGoogle Scholar
  9. 9.
    Leung FW, Golub M, Tuck M, Yip I, Go VLW (2001) Stimulation of intestinal mucosal afferent nerves increases superior mesenteric artery and decreases mesenteric adipose tissue blood flow. Dig Dis Sci 46(6):1217–1222PubMedCrossRefGoogle Scholar
  10. 10.
    Haywood JR, Shaffer RA, Fastenow C, Fink GD, Brody MJ (1981) Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat. Am J Physiol 241:H273–H278PubMedGoogle Scholar
  11. 11.
    Van Orden DE, Farley DB, Fastenow C, Brody MJ (1984) A technique for monitoring blood flow changes with miniaturized Doppler flow probes. Am J Physiol 247:H1005–H1009PubMedGoogle Scholar
  12. 12.
    Koerfer J, Bauerfeind P, Armstrong D, Blum AL (1993) Continuous measurement of rat gastric blood flow using Doppler flowmeter. Am J Physiol 264:G686–G692PubMedGoogle Scholar
  13. 13.
    Leung FW, Guth PH, Scremin OU, Golanska EM, Kauffman GL, Jr (1984) Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit. Gastroenterology 87:28–36PubMedGoogle Scholar
  14. 14.
    Leung FW, Morishita T, Livingston EH, Reedy T, Guth PH (1987) Reflectance spectrophotometry for the assessment of gastroduodenal mucosal perfusion. Am J Physiol 252:G797–G804PubMedGoogle Scholar
  15. 15.
    Leung FW (1990) Comparison of duodenal blood flow by hydrogen gas clearance and laser Doppler flowmetry. Scand J Gastroenterol 25:429–434PubMedGoogle Scholar
  16. 16.
    Leung FW, Itoh M, Hirabayashi K, Guth PH (1985) Role of blood flow in gastric and duodenal mucosal injury in the rat. Gastroenterology 88:281–289PubMedGoogle Scholar
  17. 17.
    Leung FW, Guth PH (1985) Dissociated effects of somatostatin on gastric acid secretion and mucosal blood flow. Am J Physiol 248:G337–G341PubMedGoogle Scholar
  18. 18.
    Leung FW, Robert A, Guth PH (1985) Gastric mucosal blood flow in rats after administration of 16, 16 dmPGE2 given in a cytoprotective dose. Gastroenterology 88:1948–1953PubMedGoogle Scholar
  19. 19.
    Robert ME, Leung FW, Guth PH (1986) Nicotine and smoking do not decrease basal gastric mucosal blood flow in anesthetized rats. Dig Dis Sci 31:530–534PubMedCrossRefGoogle Scholar
  20. 20.
    Leung FW, Kauffman GL, Jr Washington J, Scremin OU, Guth PH (1986) Blood flow limitation of stimulated gastric acid secretion in the rat. Am J Physiol 250:G794–G799PubMedGoogle Scholar
  21. 21.
    Whittle BJR, Morishita T, Ohya Y, Leung FW, Guth PH (1986) Microvascular actions of platelet-activating factor on rat gastric mucosa and submucosa. Am J Physiol 251:G772–G778PubMedGoogle Scholar
  22. 22.
    Livingston EH, Ready T, Leung FW, Guth PH (1989) Computerized curve fitting in the analysis of hydrogen gas clearance curves for blood flow determination. Am J Physiol 257:G668–G675PubMedGoogle Scholar
  23. 23.
    Thiefin G, Tache Y, Leung FW, Guth PH (1989) CNS action of thyrotropin-releasing hormone to increase gastric mucosal blood flow in rat. Gastroenterology 97:405–411PubMedGoogle Scholar
  24. 24.
    Endoh K, Kao J, Domek MJ, Leung FW (1993) Mechanism of gastric hyperemia induced by intragastric hypertonic saline in rats. Gastroenterology 104:114–121PubMedGoogle Scholar
  25. 25.
    Iwata F, Leung FW (1995) Tobacco cigarette smoke aggravates gastric ulcer in rats by attenuation of ulcer margin hyperemia. Am J Physiol 268:G153–G160PubMedGoogle Scholar
  26. 26.
    Iwata F, Scremin OU, Leung FW (1995) Tobacco cigarette smoke attenuates duodenal ulcer margin hyperemia in rat—comparison of IAP clearance and hydrogen gas clearance techniques for measurements of gastrointestinal blood flow. Dig Dis Sci 40:1112–1117PubMedCrossRefGoogle Scholar
  27. 27.
    Li MKK, Tsui CP, Sung JJY, Scremin OU, Leung FW (1998) Potassium channels participate in gastric mucosal protection in rats with partial portal vein ligation. Hepatology 27:1530–1535PubMedCrossRefGoogle Scholar
  28. 28.
    West DB, Prinz WA. Greenwood MR (1989) Regional changes in adipose tissue blood flow and metabolism in rats after a meal. Am J Physiol 257(4; Pt 2):R711–R716PubMedGoogle Scholar
  29. 29.
    Cui J, Himms-Hagen J (1992) Long-term decrease in body fat and in brown adipose tissue in capsaicin-desensitized rats. Am J Physiol 262:R568–R573PubMedGoogle Scholar
  30. 30.
    Shepherd AP, Riedel GL (1982) Continuous measurement of intestinal mucosal blood flow by laser-Doppler velocimetry. Am J Physiol 242(6):G668–G672PubMedGoogle Scholar
  31. 31.
    Chung SCS, Leung JWC, Leung FW (1990) Effect of submucosal epinephrine injection on local gastric blood flow: a study using laser Doppler flowmetry and reflectance spectrophotometry. Dig Dis Sci 35:1008–1011PubMedCrossRefGoogle Scholar
  32. 32.
    Leung FW, Koo A (1991) Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. Dig Dis Sci 36:727–732PubMedCrossRefGoogle Scholar
  33. 33.
    Leung FW, Chan CC (2006) Intragastric nitroglycerin in a vasodilatory dose attenuates acidified aspirin-induced gastric mucosal injury. Dig Dis Sci (in press)Google Scholar
  34. 34.
    Iwase M, Ichikawa K, Tashiro K, Iino K, Shinohara N, Ibayashi S, Yoshinari M, Fujishima M (2000) Effects of monosodium glutamate-induced obesity in spontaneously hypertensive rats vs. Wistar Kyoto rats: serum leptin and blood flow to brown adipose tissue. Hypertens Res Clin Exp 23(5):503–510Google Scholar
  35. 35.
    Figus A, Mosahebi A, Ramakrishnan V (2006) Microcirculation in DIEP flaps: a study of the haemodynamics using laser Doppler flowmetry and lightguide reflectance spectrophotometry. J Plast Reconstr Aesth Surg 59(6):604–612CrossRefGoogle Scholar
  36. 36.
    Afonso LC, Edelson GW, Sowers JR (1997) Metabolic abnormalities in hypertension. Cur Opinion Nephrol Hypertens 6:219–223CrossRefGoogle Scholar
  37. 37.
    Serrano RM (1998) Relationship between obesity and the increased risk of major complications in non-insulin-dependent diabetes mellitus. Eur J Clin Invest 28(Suppl 2):14–17CrossRefGoogle Scholar
  38. 38.
    Pascot A, Despres JP, Lemieux I, et al. (2001) Deterioration of the metabolic risk profile in women. Respective contributions of impaired glucose tolerance and visceral fat accumulation. Diabetes Care 24(5):902–908PubMedCrossRefGoogle Scholar
  39. 39.
    Sharma AM (2006) The obese patient with diabetes mellitus: from research targets to treatment options. Am J Med 119(5; Suppl 1):S17–S23PubMedCrossRefGoogle Scholar
  40. 40.
    Holzer P (1991) Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43:143–201PubMedGoogle Scholar
  41. 41.
    Wahlqvist ML, Wattanapenpaiboon N (2001) Hot foods—unexpected help with energy balance? Lancet 358(9279):348–349PubMedCrossRefGoogle Scholar
  42. 42.
    Interdepartment Committee on Nutrition for National Defense (1962) Nutrition survey—the Kingdom of Thailand. U.S. Government Priniting Office, Washington, DC, pp 57–59Google Scholar
  43. 43.
    Donnerer J, Amann R, Schuligoi R, Lembeck F (1990) Absorption and metabolism of capsaicinoids following intragastric administration in rats. Naunyn-Schmiedebergs Arch Pharmacol 342(3):357–361PubMedGoogle Scholar
  44. 44.
    Rozsa Z, Jacobson ED (1989) Capsaicin-sensitive nerves are involved in bile-oleate-induced intestinal hyperemia. Am J Physiol 256(3; Pt 1):G476–G481PubMedGoogle Scholar
  45. 45.
    Tamura CS, Ritter RC (1997) Intraintestinal capsaicin transiently reduces CGRP-like immunoreactivity in rat submucosal plexus. Brain Res 770(1–2):248–255PubMedCrossRefGoogle Scholar
  46. 46.
    Crandall DL, Hausman GJ, Kral JG (1997) A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives. Microcirculation 4(2):211–232PubMedCrossRefGoogle Scholar
  47. 47.
    Rofe AM, Williamson DH (1983) Mechanism for the ‘anti-lipolytic’ action of vasopressin in the starved rat. Biochem J 212(3):899–902PubMedGoogle Scholar
  48. 48.
    Jensen MD, Sarr MG, Dumesic DA, Southorn PA, Levine JA (2003) Regional uptake of meal fatty acids in humans. Am J Physiol 285(6):E1282–E1288Google Scholar
  49. 49.
    Nopanitaya W (1973) Long term effects of capsaicin on fat absorption and the growth of the rat. Growth 37(3):269–279PubMedGoogle Scholar
  50. 50.
    Saito A, Nakamura K, Hori Y, Yamamoto M (1999) Effects of capsaicin on serum triglycerides and free fatty acid in olive oil treated rats. Int J Vitamin Nutr Res 69(5):337–340CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Felix W. Leung
    • 1
    • 3
    • 5
    • 8
  • Vay Liang W. Go
    • 4
    • 5
  • Oscar U. Scremin
    • 2
    • 3
    • 5
  • Andre Obenaus
    • 6
  • Michael L. Tuck
    • 1
    • 3
    • 5
  • Michael S. Golub
    • 1
    • 3
    • 5
  • Peter Eggena
    • 1
    • 3
    • 5
  • Joseph W. Leung
    • 7
  1. 1.Research and Medical ServicesSepulveda Ambulatory Care Center and Nursing HomeSepulvedaUSA
  2. 2.West Los Angeles Veterans Affairs Medical CenterWest Los AngelesUSA
  3. 3.Veterans Affairs Greater Los Angeles Healthcare SystemSepulvedaUSA
  4. 4.Department of Medicine, University of California, Los AngelesLos AngelesUSA
  5. 5.David Geffen School of Medicine at University of California, Los AngelesLos AngelesUSA
  6. 6.Department of Radiation MedicineLoma Linda University School of MedicineLoma LindaUSA
  7. 7.Sacramento Veterans Affairs Medical CenterNorthern California Healthcare System, and University of California, DavisSacramentoUSA
  8. 8.Division of Gastroenterology (111G)Sepulveda Ambulatory Care Center and Nursing Home, Veterans Affairs Greater Los Angeles Healthcare SystemSepulvedaUSA

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