Acta Diabetologica

, Volume 56, Issue 2, pp 227–236 | Cite as

Duodenal adipose tissue is associated with obesity in baboons (Papio sp): a novel site of ectopic fat deposition in non-human primates

  • Paul B. HigginsEmail author
  • Franco FolliEmail author
  • Marcia C. R. Andrade
  • Jaydee Foster
  • Vicki Mattern
  • Rita Paroni
  • Natalia Schlabritz-Loutsevitch
  • V. Saroja Voruganti
  • Shyamesh Kumar
  • Rodolfo Guardado-Mendoza
  • Gaetano Bulfamante
  • Paolo Fiorina
  • Antonio E. Pontiroli
  • Gene B. Hubbard
  • Michael Owston
  • Edward J. DickJr.
  • Anthony G. Comuzzie
Original Article



Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity.


Duodenal tissues were collected from aged (21.2 ± 1.3 years, 19.5 ± 3.1 kg, n = 39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated.


Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 ± 6.93%) and was correlated with AC (r = 0.60, p < 0.001), weight (r = 0.38, p = 0.02), leptin (r = 0.63, p < 0.001), adiponectin (r = − 0.32, p < 0.05), and triglyceride (r = 0.41, p = 0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 µm2, p = 0.02).


Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition.


Non human primates Baboons Insuline resistance Ectopic fat deposition Adipose tissue Duodenum Gastrointestinal tract 



These studies were supported by CAPES and the NIH grants P51 RR013986 and C06 RR014578.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to disclose.

Human and animal rights

This research was undertaken in compliance with the “Principles of laboratory animal care” (NIH publication No. 86-23, revised 1985), as well as with the National Guidelines and the American Society of Primatologists principles for ethical treatment of Non-Human Primates.

Informed consent

For this type of study formal consent is not required.

Supplementary material

592_2019_1286_MOESM1_ESM.docx (9.6 mb)
Supplementary material 1 (DOCX 9782 KB)
592_2019_1286_MOESM2_ESM.docx (9.6 mb)
Supplementary material 2 (DOCX 9782 KB)


  1. 1.
    Shulman GI (2014) Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 371:1131–1141CrossRefGoogle Scholar
  2. 2.
    Fabbrini E, Magkod F, Mohammed BS et al. (2009) Intrahepatic fat, not visceral fat, is linked with the metabolic complications of obesity. Proc Natl Acad Sci U S A 106:15430–15435CrossRefGoogle Scholar
  3. 3.
    Lim S, Meigs JB (2014) Links between ectopic fat and vascular disease in humans. Arterioscler Thromb Vasc Biol 34:1820–1826CrossRefGoogle Scholar
  4. 4.
    Montani JP, Carroll JF, Dwyer TM, Antic V, Yang Z, Dulloo AG (2004) Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases. Int J Obes 28:S58–S65CrossRefGoogle Scholar
  5. 5.
    Singh RG, Yoon HD, Wu LM, Lu J, Plank LD, Petrov MS (2017) Ectopic fat accumulation in the pancreas and its clinical relevance: a systematic review, meta-analysis, and meta-regression. Metabolism 69:1–13CrossRefGoogle Scholar
  6. 6.
    Bifari F, Manfrini R, Dei Cas M, Berra C, Siano M, Zuin M, Paroni R, Folli F (2018) Multiple target tissue effects of GLP-1 analogues on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Pharmacol Res 137:219–229CrossRefGoogle Scholar
  7. 7.
    Harisinghani MG, Wittenberg J, Lee W, Chen S, Gutierrez AL, Mueller PR (2003) Bowel wall fat halo sign in patients without intestinal disease. Am J Roentgenol 181:781–784CrossRefGoogle Scholar
  8. 8.
    Hauret L, Aït-Ameur A, Dion A, Bellaïche R, Mennecier D, Boyer B (2004) The fat halo sign in the small intestine: diagnostic implications? J Radiol 85:1947–1949CrossRefGoogle Scholar
  9. 9.
    Gervaise A, Naulet P, Gervaise-Henry C, Junca-Laplace C, Pernin M, Lapierre-Combes M (2016) Gastric wall fatty infiltration in patients without overt gastrointestinal disease. Am J Roentgenol 206:734–739CrossRefGoogle Scholar
  10. 10.
    Ahualli J (2007) The fat halo sign. Radiology 242:945–946CrossRefGoogle Scholar
  11. 11.
    Amitai MM, Arazi-Kleinman T, Avidan B, Apter S, Konen E, Biegon A, Hertz M (2007) Fat halo sign in the bowel wall of patients with Crohn’s disease. Clin Radiol 62:994–997CrossRefGoogle Scholar
  12. 12.
    Giaslakiotis K, Baird A, Warren BF (2008) Submucosal fat deposition in a patient with Crohn’s disease: the fat halo sign. Histopathology 53:611–612Google Scholar
  13. 13.
    Schwarz J, Studler U, Bongartz G (2006) Fat halo sign of the colon: not only in patients with inflammatory bowel disease an illustrated case-report. Praxis (Bern 1994) 95:197–200CrossRefGoogle Scholar
  14. 14.
    Mesa H, Drawz S, Dykoski R, Manivel JC (2015) Morphometric measurement of submucosal thickness in areas of fat deposition in the terminal ileum and colonic sections, with correlation with body mass index, weight and age: a male autopsy study. Histopathology 67:457–463CrossRefGoogle Scholar
  15. 15.
    Higgins PB, Rodriguez PJ, Voruganti VS, Mattern V, Bastarrachea RA, Rice K, Raabe T, Comuzzie AG (2014) Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism. Am J Phys Anthropol 153:9–14CrossRefGoogle Scholar
  16. 16.
    Chavez AO, Lopez-Alvarenga JC, Tejero ME, Triplitt C, Bastarrachea RA, Sriwijitkamol A, Tantiwong P, Voruganti VS, Musi N, Comuzzie AG, DeFronzo RA, Folli F (2008) Physiological and molecular determinants of insulin action in the baboon. Diabetes 57:899–908CrossRefGoogle Scholar
  17. 17.
    Quinn AR, Blanco CL, Perego C, Finzi G, La Rosa S, Capella C, Guardado-Mendoza R, Casiraghi F, Gastaldelli A, Johnson M, Dick EJ Jr, Folli F (2012) The ontogeny of the endocrine pancreas in the fetal/newborn baboon. J Endocrinol 214(3):289–299CrossRefGoogle Scholar
  18. 18.
    Official Methods of Analysis (1990). In: Helrich K (ed), The association of official analytical chemists, 15th edn. Arlington, VA, USA, p 79Google Scholar
  19. 19.
    Rasband WS, ImageJ US National Institutes of Health, Bethesda, Maryland, USA., 1997–2016. Accessed 16 May 2016
  20. 20.
    Liu RX, Kuang J, Gong Q, Hou XL (2003) Principal component regression analysis with SPSS. Comput Methods Programs Biomed 71:141–147CrossRefGoogle Scholar
  21. 21.
    Comuzzie AG, Cole SA, Martin L, Carey KD, Mahaney MC, Blangero J, VandeBerg JL (2003) The baboon as a nonhuman primate model for the study of the genetics of obesity. Obes Res 11:75–80CrossRefGoogle Scholar
  22. 22.
    Guardado-Mendoza R, Davalli AM, Chavez AO, Hubbard GB, Dick EJ, Majluf-Cruz A, Tene-Perez CE, Goldschmidt L, Hart J, Perego C, Comuzzie AG, Tejero ME, Finzi G, Placidi C, La Rosa S, Capella C, Halff G, Gastaldelli A, DeFronzo RA, Folli F (2009) Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons. Proc Natl Acad Sci U S A 106:13992–13997CrossRefGoogle Scholar
  23. 23.
    Higgins PB, Bastarrachea RA, Lopez-Alvarenga JC, Garcia-Forey M, Proffitt JM, Voruganti VS, Tejero ME, Mattern V, Haack K, Shade RE, Cole SA, Comuzzie AG (2010) Eight week exposure to a high sugar high fat diet results in adiposity gain and alterations in metabolic biomarkers in baboons (Papio hamadryas sp.). Cardiovasc Diabetol 9:71CrossRefGoogle Scholar
  24. 24.
    Kamath S, Chavez AO, Gastaldelli A, Casiraghi F, Halff GA, Abrahamian GA, Davalli AM, Bastarrachea RA, Comuzzie AG, Guardado-Mendoza R, Jimenez-Ceja LM, Mattern V, Paez AM, Ricotti A, Tejero ME, Higgins PB, Rodriguez-Sanchez IP, Tripathy D, DeFronzo RA, Dick EJ Jr, Cline GW, Folli F (2011) Coordinated defects in hepatic long chain fatty acid metabolism and triglyceride accumulation contribute to insulin resistance in non-human primates. PLoS One 6: e27617CrossRefGoogle Scholar
  25. 25.
    Dick EJ Jr, Owston M, David JM, Sharp RM, Rouse S, Hubbard GB (2014) Mortality in captive baboons (Papio spp.): a 23 year study. J Med Primatol 43(3):169–196CrossRefGoogle Scholar
  26. 26.
    Guardado Mendoza R, Perego C, Finzi G, La Rosa S, Capella C, Jimenez-Ceja LM, Velloso LA, Saad MJ, Sessa F, Bertuzzi F, Moretti S, Dick EJ Jr, Davalli AM, Folli F (2015) Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas). Diabetologia 58(8):1814–1826CrossRefGoogle Scholar
  27. 27.
    Folli F, La Rosa S, Finzi G, Davalli AM, Galli A, Dick EJ Jr, Perego C, Mendoza RG (2018) Pancreatic islet of Langerhans’ cytoarchitecture and ultrastructure in normal glucose tolerance and in type 2 diabetes mellitus. Diabetes Obes Metab Suppl 2:137–144CrossRefGoogle Scholar
  28. 28.
    Chavez AO, Gastaldelli A, Guardado-Mendoza R, Lopez-Alvarenga JC, Leland MM, Tejero ME, Sorice G, Casiraghi F, Davalli A, Bastarrachea RA, Comuzzie AG, DeFronzo RA, Folli F (2009) Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome Baboons. Cardiovasc Diabetol 8:22CrossRefGoogle Scholar
  29. 29.
    Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ (1998) The stomach is a source of leptin. Nature 394:790–793CrossRefGoogle Scholar
  30. 30.
    Yarandi SS, Hebbar G, Sauer CG, Cole CR, Ziegler TR (2001) Diverse roles of leptin in the gastrointestinal tract: modulation of motility, absorption, growth, and inflammation. Nutrition 27:269–275CrossRefGoogle Scholar
  31. 31.
    Häring HU (2016) Novel phenotypes of prediabetes? Diabetologia 59:1806–1818CrossRefGoogle Scholar
  32. 32.
    Heni M, Machann J, Staiger H, Schwenzer NF, Peter A, Schick F, Claussen CD, Stefan N, Häring HU, Fritsche A (2010) Pancreatic fat is negatively associated with insulin secretion in individuals with impaired fasting glucose and/or impaired glucose tolerance: a nuclear magnetic resonance study. Diabetes Metab Res Rev 26:200–205CrossRefGoogle Scholar
  33. 33.
    Mills SE (ed) (2007) Histology for pathologists, 3rd edn. Lippincott, Williams, & Wilkins, Philadelphia, p 611Google Scholar
  34. 34.
    Laforest S, Labrecque J, Michaud A, Cianflone K, Tchernof A (2015) Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction. Crit Rev Clin Lab Sci 52:301–313CrossRefGoogle Scholar
  35. 35.
    Hanani M, Nissan A, Freund HR (2007) Innervation of submucosal adipocytes in the human colon. Neurosci Lett 428:7–10CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • Paul B. Higgins
    • 1
    Email author
  • Franco Folli
    • 2
    • 3
    Email author
  • Marcia C. R. Andrade
    • 4
  • Jaydee Foster
    • 1
  • Vicki Mattern
    • 1
  • Rita Paroni
    • 5
  • Natalia Schlabritz-Loutsevitch
    • 6
  • V. Saroja Voruganti
    • 7
  • Shyamesh Kumar
    • 8
  • Rodolfo Guardado-Mendoza
    • 9
  • Gaetano Bulfamante
    • 10
    • 11
  • Paolo Fiorina
    • 12
  • Antonio E. Pontiroli
    • 13
  • Gene B. Hubbard
    • 8
  • Michael Owston
    • 8
  • Edward J. DickJr.
    • 8
  • Anthony G. Comuzzie
    • 14
  1. 1.Department of GeneticsTexas Biomedical Research InstituteSan AntonioUSA
  2. 2.Endocrinology and Metabolism, Department of Health ScienceUniversity of MilanMilanItaly
  3. 3.UOSD of Diabetes and Metabolic DisordersASST Santi Paolo e CarloMilanItaly
  4. 4.Center for Laboratory Animal BreedingOswaldo Cruz FoundationRio de JaneiroBrazil
  5. 5.Laboratory of Clinical Biochemistry and Mass Spectrometry, Department of Health ScienceUniversity of MilanMilanItaly
  6. 6.Department of Obstetrics and Gynecology, School of MedicineTexas Tech University Health Sciences Center at the Permian BasinOdessaUSA
  7. 7.Nutrition Research Institute, Department of NutritionUniversity of North Carolina at Chapel HillKannapolisUSA
  8. 8.Southwest National Primate Research CenterTexas Biomedical Research InstituteSan AntonioUSA
  9. 9.Metabolic Research LaboratoryUniversity of GuanajuatoGuanajuatoMexico
  10. 10.Pathological Anatomy, Department of Health ScienceUniversity of MilanoMilanItaly
  11. 11.ASST Santi Paolo e CarloMilanItaly
  12. 12.Department of Biomedical and Clinical Sciences“L. Sacco”, University of MilanMilanItaly
  13. 13.Department of Health ScienceUniversity of MilanMilanItaly
  14. 14.The Obesity SocietyMarylandUSA

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