Preview

Translational Medicine

Advanced search

Gastrointestinal morphofunctional changes in experimental obesity models

https://doi.org/10.18705/2311-4495-2026-13-1-82-91

EDN: OMGPBT

Abstract

Obesity is a global health problem whose incidence is steadily increasing. Modern lifestyles, characterized by changing dietary preferences and low levels of physical activity, are key factors in the development of obesity and overweight. Obesity increases the risk of numerous gastrointestinal (GI) diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, functional digestive disorders, and others. The pathogenesis of these conditions includes chronic low-grade inflammation, increased intestinal barrier permeability, and changes in the intestinal microflora. The purpose of this article is to describe and systematize high-calorie diets and to study the morphological and pathophysiological mechanisms by which these diets influence the gastrointestinal tract. This review examines the main types of diets used to model obesity in laboratory animals: high-fat, high-carbohydrate, with a choice of fats or carbohydrates, combined (“cafeteria diet”, “Western diet”), and models of psychogenic overeating. Histological features of the gastrointestinal tract wall of obese rats are represented by changes in the mucosa (a decrease in the number of PAS-positive goblet cells) and the lamina propria (an increase in the number of neutrophils, lymphocytes, macrophages, and collagen fibers). In addition, increased concentrations of IL-1β, IL-6, IL-8, TNF and monocyte chemotactic protein (MCP-1), and malondialdehyde (MDA) were detected in the colon wall. Obesity and excess body weight have been shown to impact structural components of the nervous system (hyperactivation of enteric ganglia, disruption of the autonomic nervous system, etc.), leading to impaired gastrointestinal motility.

Experimental studies demonstrate that high-calorie diets alter the histological characteristics and motility of the gastrointestinal tract in laboratory animals, causing structural damage and disruption of innervation of the digestive organs. This indicates the need for further research to identify the mechanisms underlying the development of obesity complications and develop effective preventive measures.

About the Authors

Valeria E. Menshchikova
Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” of the Ministry of Health of the Russian Federation
Russian Federation

Valeria E. Menshchikova, Postgraduate Student in Pediatrics at the Department of Propaedeutics of Childhood Diseases,

52, pr. Krasny, Novosibirsk, 630091.


Competing Interests:

The authors declare no conflict of interest.



Anastasiya E. Karavozova
Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” of the Ministry of Health of the Russian Federation
Russian Federation

Anastasiya E. Karavozova, 2-year Instructor in Pediatrics at the Department of Pediatric Diseases,

Novosibirsk.


Competing Interests:

The authors declare no conflict of interest.



Tatiana V. Kartseva
Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” of the Ministry of Health of the Russian Federation
Russian Federation

Tatiana V. Kartseva, MD, DSc, Associate Professor, Head of the Department of Propaedeutics of Childhood Diseases,

Novosibirsk .


Competing Interests:

The authors declare no conflict of interest.



Svetlana V. Zalavina
Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” of the Ministry of Health of the Russian Federation
Russian Federation

Svetlana V. Zalavina, MD, DSc, Associate Professor, Head of the Department of Histology, Embryology and Cytology named after Prof. M.Ya. Subbotin,

Novosibirsk.


Competing Interests:

The authors declare no conflict of interest.



Tatyana I. Ryabichenko
Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” of the Ministry of Health of the Russian Federation; Federal State Budgetary Scientific Institution “Federal Research Center for Fundamental and Translational Medicine” (FRC)
Russian Federation

Tatyana I. Ryabichenko, MD, DSc, Leading Researcher, Laboratory of Immunology, Research Institute of Experimental and Clinical Medicine (FRC),

Novosibirsk.


Competing Interests:

The authors declare no conflict of interest.



Daria V. Eliseeva
Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” of the Ministry of Health of the Russian Federation
Russian Federation

Daria V. Eliseeva, Assistant at the Department of Propaedeutics of Childhood Diseases,

Novosibirsk.


Competing Interests:

The authors declare no conflict of interest.



References

1. Drapkina OM, Kim OT. Obesity — an epidemic of the Anthropocene epoch: monograph. Moscow: ROPNIZ, Silicea-Polygraph LLC; 2024. (In Russ.)

2. Bondareva EA, Troshina EA. Obesity. Reasons, features and prospects. Obesity and metabolism. 2024;21(2):174‒187. (In Russ.) https://doi.org/10.14341/omet13055

3. Levin BE, Geary N, Lutz TA. The (dys)regulation of energy storage in obesity. Physiol Rev. 2025;105(3):803‒895. https://doi.org/10.1152/physrev.00002.2024

4. Colamatteo A, Fusco C, Matarese A, Matarese G. Obesity and autoimmunity epidemic: the role of immunometabolism. Annu Rev Nutr. 2025;45(1):115‒140. https://doi.org/10.1146/annurev-nutr-111324-122456

5. Koskinas KC, Van Craenenbroeck EM, Antoniades C, et al. ESC Scientific Document Group. Obesity and cardiovascular disease: an ESC clinical consensus statement. Eur Heart J. 2024;45(38):4063‒4098. https://doi.org/10.1093/eurheartj/ehae508

6. Zhang X, Ha S, Lau HC, Yu J. Excess body weight: novel insights into its roles in obesity comorbidities. Semin Cancer Biol. 2023;92:16‒27. https://doi.org/10.1016/j.semcancer.2023.03.008

7. Chandrasekaran P, Weiskirchen R. The role of obesity in type 2 diabetes mellitus-an overview. Int J Mol Sci. 2024;25(3):1882. https://doi.org/10.3390/ijms25031882

8. Gonzalez-Gutierrez L, Motiño O, Barriuso D, et al. Obesity-associated colorectal cancer. Int J Mol Sci. 2024; 25(16):8836. https://doi.org/10.3390/ijms25168836

9. Bischoff SC, Barazzoni R, Busetto L, et al. European guideline on obesity care in patients with gastrointestinal and liver diseases — Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline. United European Gastroenterol J. 2022;10(7):663‒720. https://doi.org/10.1002/ueg2.12280

10. Choe Y. Obesity and upper gastrointestinal diseases. Korean J Gastroenterol. 2024;83(3):81‒86. https://doi.org/10.4166/kjg.2024.015

11. Mahadeva S. Obesity and functional gastrointestinal disorders: What is the link? J Gastroenterol Hepatol. 2023; 38(3):344‒345. https://doi.org/10.1111/jgh.16158

12. Zia JK, Lenhart A, Yang PL, et al. Risk factors for abdominal pain-related disorders of gut-brain interaction in adults and children: a systematic review. Gastroenterology. 2022;163:995–1023e3.

13. Andreev DN, Kucheryavyi YuA. Obesity as a risk factor for diseases of the digestive system. Therapeutic Archive. 2021;93(8):954–962. (In Russ.) https://doi.org/10.26442/00403660.2021.08.200983

14. Black CJ, Drossman DA, Talley NJ, et al. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020;396:1664–1674. https://doi.org/10.1016/S0140-6736(20)32115-2

15. Raybould HE. Gut microbiota, epithelial function and derangements in obesity. J Physiol. 2012;590:441–446. https://doi.org/10.1113/jphysiol.2011.222133

16. Almeida PP, Valdetaro L, Thomasi BBM, et al. High-fat diets on the enteric nervous system: Possible interactions and mechanisms underlying dysmotility. Obes Rev. 2022;23(4):e13404. https://doi.org/10.1111/obr.13404

17. Guimarães AGC, Lopes LES, Capelassi AN, et al. Morphological alterations in gastrointestinal organs of western-diet obese rats submitted to vertical sleeve gastrectomy or Roux-en-Y gastric bypass. An Acad Bras Cienc. 2021;93(4):e20200884. https://doi.org/10.1590/0001-3765202120200884

18. Mo X, Cheng R, Shen L, et al. High-fat diet induces sarcopenic obesity in natural aging rats through the gut-trimethylamine N-oxide-muscle axis. J Adv Res. 2025;70:405‒422. https://doi.org/10.1016/j.jare.2024.05.015

19. Bayrasheva VK, Pchelin IU, Egorova AE, et al. Experimental models of nutritional obesity in rats. Juvenis Scientia. 2019;(9‒10):8‒13. (In Russ.) https://doi.org/10.32415/jscientia.2019.09-10.02

20. Makarova MN, Makarov VG. Diet-induced models of metabolic disorders. Message 2: Experimental obesity. Laboratory animals for scientific research. 2018;2. (In Russ.). https://doi.org/10.29296/2618723X-2018-02-05

21. Kovaleva MA, Gushchin YaA, Makarova МN, et al. Comparative study of the use of high-calorie diets enriched by different number of lipids for modeling metabolic syndrome. Laboratory Animals for Science. 2019;(1):55‒65. (In Russ.) https://doi.org/10.29296/2618723X-2019-01-04

22. Kwitek AE. Rat models of metabolic syndrome. Methods Mol Biol. 2019;2018:269‒285. https://doi.org/10.1007/9781-4939-9581-3_13

23. Sadowska J, Bruszkowska M. Comparing the effects of sucrose and high-fructose corn syrup on lipid metabolism and the risk of cardiovascular disease in male rats. Acta Sci Pol Technol Aliment. 2017;16(2):231‒240. https://doi.org/10.17306/J.AFS.0482.

24. Chernysheva MB, Tsvetkov IS, Diatroptov ME. Morphological changes in the internal organs and metabolic disorders during experimental alimentary obesity. Clinical and experimental morphology. 2016;1(17):44‒51. (In Russ.) https://www.elibrary.ru/zfcatd

25. Barrett P, Mercer JG, Morgan PJ. Preclinical models for obesity research. Dis Model Mech. 2016;9(11):1245‒1255. https://doi.org/10.1242/dmm.026443

26. Balbo SL, Ribeiro RA, Mendes MC, et al. Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release. J Physiol Biochem. 2016;72(4):625‒633. https://doi.org/10.1007/s13105-016-0501-9

27. Chernysheva MB, Makarova MA, Tsvetkov IS. Morphological changes of the internal organs of rats after long-term excessive consumption of carbohydrates and fats. Morphological newsletter. 2014;22(3):74‒78. (In Russ.) https://doi.org/10.20340/mv-mn.2014.0(3):74‒78

28. Gentile D, Fornai M, Colucci R, et al. The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity. PLoS One. 2018;13(4):e0195502. https://doi.org/10.1371/journal. pone.0195502

29. Letafati A, Najafi S, Mottahedi M, et al. MicroRNA let-7 and viral infections: focus on mechanisms of action. Cell Mol Biol Lett. 2022;27(1):14. https://doi.org/10.1186/s11658-022-00317-9

30. Antonioli L, Caputi V, Fornai M, et al. Interplay between colonic inflammation and tachykininergic pathways in the onset of colonic dysmotility in a mouse model of diet-induced obesity. Int J Obes (Lond). 2019;43(2):331‒343. https://doi.org/10.1038/s41366-018-0166-2

31. D’Antongiovanni V, Benvenuti L, Fornai M, et al. Glial A2B adenosine receptors modulate abnormal tachykininergic responses and prevent enteric inflammation associated with high fat diet-induced obesity. Cells. 2020 May 18;9(5):1245. https://doi.org/10.3390/cells9051245

32. Hamilton MK, Boudry G, Lemay DG, Raybould HE. Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent. Am J Physiol Gastrointest Liver Physiol. 2015;308(10):G840‒851. https://doi.org/10.1152/ajpgi.00029.2015

33. Teixeira LG, Leonel AJ, Aguilar EC, et al. The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation. Lipids Health Dis. 2011;10:204. https://doi.org/10.1186/1476-511X-10-204

34. Mo X, Cheng R, Shen L, et al. High-fat diet induces sarcopenic obesity in natural aging rats through the gut-trimethylamine N-oxide-muscle axis. J Adv Res. 2025;70:405‒422. https://doi.org/10.1016/j.jare.2024.05.015

35. Gentile D, Fornai M, Colucci R, et al. The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity. PLoS One. 2018;13(4):e0195502. https://doi.org/10.1371/journal.pone.0195502

36. Mushref MA, Srinivasan S. Effect of high fat-diet and obesity on gastrointestinal motility. Ann Transl Med. 2013;1(2):14. https://doi.org/10.3978/j.issn.2305-5839.2012.11.01

37. KhiaosaArd R, Zebeli Q. Diet-induced inflammation: from gut to metabolic organs and the consequences for the health and longevity of ruminants. Res Vet Sci. 2018;120:17–27. https://doi.org/10.1016/j.rvsc.2018.08.005

38. McMenamin CA, Clyburn C, Browning KN. Highfat diet during the perinatal period induces loss of myenteric nitrergic neurons and increases enteric glial density, prior to the development of obesity. Neuroscience. 2018;393:369–380. https://doi.org/10.1016/j.neuroscience.2018.09.033

39. Yavuz Y, Kumral ZN, Memi G, et al. Serum leptin, obestatin, and ghrelin levels and gastric emptying rates of liquid and solid meals in non-obese rats with roux-en-Y bypass surgery or prosthesis placement: implications for the role of vagal afferents. Obes Surg. 2017;27:1037–1046. https://doi.org/10.1007/s11695-016-2420-9

40. Antonioli L, Caputi V, Fornai M, et al. Interplay between colonic inflammation and tachykininergic pathways in the onset of colonic dysmotility in a mouse model of diet-induced obesity. Int J Obes (Lond). 2019;43(2):331‒343. https://doi.org/10.1038/s41366-018-0166-2

41. Lefèvre MA, Godefroid Z, Soret R, Pilon N. Enteric glial cell diversification is influenced by spatiotemporal factors and source of neural progenitors in mice. Front Neurosci. 2024;18:1392703. https://doi.org/10.3389/fnins.2024.1392703

42. Khochanskij DN, Makarova OV. Current views on the structure and function of enteric nervous system. Morphological newsletter. 2015;23(1):106‒117. (In Russ.) https://doi.org/10.20340/mv-mn.2015.0(1):106-117

43. Abd El-Ghani SE, Hamed RMR, Eid RA, et al. Serum interleukin 1β and sP-selectin as biomarkers of inflammation and thrombosis, could they be predictors of disease severity in COVID 19 Egyptian patients? (a cross-sectional study). Thromb J. 2022;20(1):77. https://doi.org/10.1186/s12959-022-00428-5

44. Bhattarai Y, Fried D, Gulbransen B, et al. High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular trans-mission and smooth muscle excitability in the mouse distal colon. Am J Physiol Gastrointest Liver Physiol. 2016;311:G210– G220. https://doi.org/10.1152/ajpgi.00085.2016

45. Anitha M, Reichardt F, Tabatabavakili S, et al. Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice. Cell Mol Gastroenterol Hepatol. 2016;2:328–339. https://doi.org/10.1016/j.jcmgh.2015.12.008

46. Nezami BG, Mwangi SM, Lee JE, et al. MicroRNA 375 mediates palmitate-induced enteric neuronal damage and high-fat diet-induced delayed intestinal transit in mice. Gastroenterology. 2014;146(2):473‒483.e3. https://doi.org/10.1053/j.gastro.2013.10.053

47. Rivera LR, Leung C, Pustovit RV, et al. Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet. Neurogastroenterol Motil. 2014;26:1188–1199. https://doi.org/10.1111/nmo.12385

48. Voss U, Sand E, Olde B, Ekblad E. Enteric neuropathy can be induced by high fat diet in vivo and palmitic acid exposure in vitro. PLoS One. 2013;8:e81413. https://doi.org/10.1371/journal.pone.0081413

49. Stenkamp-Strahm CM, Nyavor YE, Kappmeyer AJ, et al. Prolonged high fat diet ingestion, obesity, and type 2 diabetes symptoms correlate with phenotypic plasticity in myenteric neurons and nerve damage in the mouse duodenum. Cell Tissue Res. 2015;361:411–426. https://doi.org/10.1007/s00441015-2132-9

50. Kaya SD, Sinen O, Bülbül M. Gastric motor dysfunction coincides with the onset of obesity in rats fed with high-fat diet. Clin Exp Pharmacol Physiol. 2021;48(4):553‒562. https://doi.org/10.1111/1440-1681.13448

51. Özdemir-Kumral ZN, Koyuncuoğlu T, Arabacı-Tamer S, et al. High-fat Diet Enhances Gastric Contractility, but Abolishes Nesfatin-1-induced Inhibition of Gastric Emptying. J Neurogastroenterol Motil. 2021;27(2):265‒278. https://doi.org/10.5056/jnm20206

52. Nyavor Y, Estill R, Edwards H, et al. Intestinal nerve cell injury occurs prior to insulin resistance in female mice ingesting a high-fat diet. Cell Tissue Res. 2019;376(3):325‒340. https://doi.org/10.1007/s00441-019-03002-0

53. Baroukh NN, Van Obberghen E. Function of microRNA-375 and microRNA-124a in pancreas and brain: Function of miR-375 and 124a in pancreas and brain. FEBS Journal. 276(22):6509–6521. https://doi.org/10.1111/j.17424658.2009.07353.x


Review

For citations:


Menshchikova V.E., Karavozova A.E., Kartseva T.V., Zalavina S.V., Ryabichenko T.I., Eliseeva D.V. Gastrointestinal morphofunctional changes in experimental obesity models. Translational Medicine. 2026;13(1):82-91. (In Russ.) https://doi.org/10.18705/2311-4495-2026-13-1-82-91. EDN: OMGPBT

Views: 224

JATS XML


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2311-4495 (Print)
ISSN 2410-5155 (Online)