High-Fat Diet and Salivary Gland Alterations: A Scoping Review
DOI:
https://doi.org/10.46862/interdental.v22i2.13850Keywords:
Inflammation, oxidative stress, saliva composition, saliva secretionAbstract
Introduction: Obesity is a growing global health concern, largely driven by high-fat diet (HFD) consumption, which promotes adipose tissue accumulation and increases metabolic disorder risk. Beyond systemic effects, obesity may impair salivary gland function, which is essential for maintaining oral homeostasis. However, evidence regarding the effects of HFDs on salivary glands remains fragmented and inconsistent. This scoping review aimed to map the literature on HFD-induced salivary gland alterations and elucidate the underlying biological mechanisms.
Review: The review followed PRISMA-ScR guidelines. Relevant studies were identified through comprehensive searches of PubMed and Scopus and screened using predefined eligibility criteria. Twenty-two studies were included. HFDs affected four major aspects of salivary gland physiology: reduced antioxidant and digestive enzyme activity; altered salivary proteins, including mucin and IgA; increased inflammatory biomarkers and oxidative stress; and morphological and functional changes, including reduced salivary secretion, fibrosis, vacuolization, inflammatory infiltration, and lipid accumulation. However, some studies reported no significant changes, suggesting that responses may vary according to gland type, HFD exposure duration, and metabolic status.
Conclusion: HFD consumption induces oxidative stress, inflammation, and structural and molecular alterations in salivary glands, potentially contributing to salivary dysfunction. Further longitudinal and translational studies are needed to clarify the underlying mechanisms and clinical implications.
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References
1. World Obesity Federation. Global Obesity Observatory [Internet]. World Obesity Day Atlases Obesity Atlas 2024 [cited 2025 Sep 15]. Available from: https://data.worldobesity.org/publications/?cat=22
2. Loos RJF, Yeo GSH. The genetics of obesity: from discovery to biology. Nat Rev Genet. 2022;23(2):120-33. DOI:10.1038/s41576-021-00414-z.
3. van der Klaauw AA, Farooqi IS. The Hunger genes: Pathways to obesity. Cell. 2015;161(1):119-32. DOI:10.1016/j.cell.2015.03.008.
4. Zolotukhin S. Metabolic hormones in saliva: origins and functions. Oral Dis. 2013;19(3):219-29. DOI:10.1111/odi.12015.
5. Savini I, Catani MV, Evangelista D, Gasperi V, Avigliano L. Obesity-associated oxidative stress: strategies finalized to improve redox state. Int J Mol Sci. 2013;14(5):10497-538. DOI:10.3390/ijms140510497.
6. Cercato C, Fonseca FA. Cardiovascular risk and obesity. Diabetol Metab Syndr. 2019;11(1):74. DOI:10.1186/s13098-019-0468-0.
7. Quaye E, Galecki AT, Tilton N, Whitney R, Briceño EM, Elkind MSV, et al. Association of obesity with cognitive decline in Black and White Americans. Neurology. 2023;100(2):e220-e231. DOI:10.1212/WNL.0000000000201367.
8. Tomah S, Alkhouri N, Hamdy O. Nonalcoholic fatty liver disease and type 2 diabetes: where do diabetologists stand? Clin Diabetes Endocrinol. 2020;6(1):9. DOI:10.1186/s40842-020-00097-1.
9. Chielle EO, Casarin JN. Evaluation of salivary oxidative parameters in overweight and obese young adults. Arch Endocrinol Metab. 2017;61(2):152-9. DOI:10.1590/2359-3997000000227.
10. de Campos MM, Kobayashi FY, Barbosa TS, Costa SS, Lucas BL, Castelo PM. Characteristics of salivary secretion in normal-weight, overweight and obese children: a preliminary study: salivary composition and excessive fat tissue. Odontology. 2014;102(2):318-24. DOI:10.1007/s10266-013-0103-8.
11. Modéer T, Blomberg CC, Wondimu B, Julihn A, Marcus C. Association between obesity, flow rate of whole saliva, and dental caries in adolescents. Obesity (Silver Spring). 2010;18(12):2367-73. DOI:10.1038/oby.2010.63.
12. Roa I, Del Sol M. Obesity, salivary glands and oral pathology. Colomb Med (Cali). 2018;49(4):280-7. DOI:10.25100/cm.v49i3.3919.
13. Zalewska A, Kossakowska A, Taranta-Janusz K, Zięba S, Fejfer K, Salamonowicz M, et al. Dysfunction of salivary glands, disturbances in salivary antioxidants and increased oxidative damage in saliva of overweight and obese adolescents. J Clin Med. 2020;9(2):548. DOI:10.3390/jcm9020548.
14. Lynge Pedersen AM, Belstrøm D. The role of natural salivary defences in maintaining a healthy oral microbiota. J Dent. 2019;80(Suppl 1):S3-12. DOI:10.1016/j.jdent.2018.08.010.
15. Zalewska A, Knaś M, Kuźmiuk A, Waszkiewicz N, Niczyporuk M, Waszkiel D, et al. Salivary innate defense system in type 1 diabetes mellitus in children with mixed and permanent dentition. Acta Odontol Scand. 2013;71(6):1493-500. DOI:10.3109/00016357.2013.773071.
16. Zalewska A, Knaś M, Waszkiewicz N, Waszkiel D, Sierakowski S, Zwierz K. Rheumatoid arthritis patients with xerostomia have reduced production of key salivary constituents. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115(4):483-90. DOI:10.1016/j.oooo.2012.10.013.
17. Zalewska A, Zięba S, Kostecka-Sochoń P, Matczuk J, Piotrowska MZ, Maciejczyk M. α-Lipoic acid supplementation salivary glands in the hyperglycaemic rats. Cell Physiol Biochem. 2022;56(Suppl 1):36-52. DOI:10.33594/000000530.
18. Maciejczyk M, Pawlukianiec C, Piotrowska MZ, Ładny JR, Zalewska A. Salivary redox biomarkers in insulin resistance: preclinical studies in an animal model. Oxid Med Cell Longev. 2021;2021:3734252. DOI:10.1155/2021/3734252.
19. Lungruammit N, Pintana H, Pratchayasakul W, Songtrai S, Kaewsuwan S, Ittichaichareon J, et al. Cyclosorus terminans extract mitigates submandibular gland changes associated with high-fat diet consumption in male rats. Arch Oral Biol. 2025;170:106127. DOI:10.1016/j.archoralbio.2024.106127.
20. Selim SA. The effect of high-fat diet-induced obesity on the parotid gland of adult male albino rats: histological and immunohistochemical study. Egypt J Histol. 2013;36(4):772-80. DOI:10.1097/01.EHX.0000437624.80956.78.
21. Ittichaicharoen J, Apaijai N, Tanajak P, Sa-Nguanmoo P, Chattipakorn N, Chattipakorn SC. Impaired mitochondria and intracellular calcium transients in the salivary glands of obese rats. Appl Physiol Nutr Metab. 2017;42(4):420-9. DOI:10.1139/apnm-2016-0545.
22. Lasisi TJ, Shittu STT, Alada AR. Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats. J Basic Clin Physiol Pharmacol. 2018;30(1):111-20. DOI:10.1515/jbcpp-2018-0006.
23. Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467-73. DOI:10.7326/M18-0850.
24. Zalewska A, Knaś M, Zendzian-Piotrowska M, Waszkiewicz N, Szulimowska J, Prokopiuk S, et al. Antioxidant profile of salivary glands in high fat diet-induced insulin resistance rats. Oral Dis. 2014;20(6):560-6. DOI:10.1111/odi.12173.
25. Martin FM, Bydlon G, Friedman JS. SOD2-deficiency sideroblastic anemia and red blood cell oxidative stress. Antioxid Redox Signal. 2006;8(7-8):1217-25. DOI:10.1089/ars.2006.8.1217.
26. Cao T, Zhou J, Liu Q, Mao T, Chen B, Wu Q, et al. Interferon-γ induces salivary gland epithelial cell ferroptosis in Sjögren's syndrome via JAK/STAT1-mediated inhibition of system Xc(-). Free Radic Biol Med. 2023;205:116-28. DOI:10.1016/j.freeradbiomed.2023.05.027.
27. Zhou J, Pathak JL, Wu L, Chen B, Cao T, Wei W, et al. Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjögren's syndrome via lipid ROS/pSTAT4/AQP5 axis. Free Radic Biol Med. 2024;218:1-15. DOI:10.1016/j.freeradbiomed.2024.04.003.
28. Zukowski P, Maciejczyk M, Matczuk J, Kurek K, Waszkiel D, Żendzian-Piotrowska M, et al. Effect of N-acetylcysteine on antioxidant defense, oxidative modification, and salivary gland function in a rat model of insulin resistance. Oxid Med Cell Longev. 2018;2018:6581970. DOI:10.1155/2018/6581970.
29. Styskal J, Van Remmen H, Richardson A, Salmon AB. Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? Free Radic Biol Med. 2012;52(1):46-58. DOI:10.1016/j.freeradbiomed.2011.10.441.
30. Maciejczyk M, Mikoluc B, Pietrucha B, Heropolitanska-Pliszka E, Pac M, Motkowski R, et al. Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome. Redox Biol. 2017;11:375-83. DOI:10.1016/j.redox.2016.12.030.
31. Amano O, Mizobe K, Bando Y, Sakiyama K. Anatomy and histology of rodent and human major salivary glands: overview of the Japan Salivary Gland Society-sponsored workshop. Acta Histochem Cytochem. 2012;45(5):241-50. DOI:10.1267/ahc.12013.
32. Zalewska A, Maciejczyk M, Szulimowska J, Imierska M, Błachnio-Zabielska A. High-fat diet affects ceramide content, disturbs mitochondrial redox balance, and induces apoptosis in the submandibular glands of mice. Biomolecules. 2019;9(12):877. DOI:10.3390/biom9120877.
33. Zalewska A, Joanna K, Zięba S, Matczuk J, Paula KS, Izabela S, et al. N-acetylcysteine supplementation did not reverse mitochondrial oxidative stress, apoptosis, and inflammation in the salivary glands of hyperglycemic rats. Nutr Diabetes. 2021;11(1):35. DOI:10.1038/s41387-021-00177-w.
34. Véret J, Coant N, Berdyshev EV, Skobeleva A, Therville N, Bailbé D, et al. Ceramide synthase 4 and de novo production of ceramides with specific N-acyl chain lengths are involved in glucolipotoxicity-induced apoptosis of INS-1 β-cells. Biochem J. 2011;438(1):177-89. DOI:10.1042/BJ20101386.
35. Cal C, Lomniczi A, Mohn CE, De Laurentiis A, Casal M, Chiarenza A, et al. Decrease in salivary secretion by radiation mediated by nitric oxide and prostaglandins. Neuroimmunomodulation. 2006;13(1):19-27. DOI:10.1159/000093194.
36. Huang H, Gao C, Wang S, Wu F, Wei J, Peng J. Bulk RNA-seq and scRNA-seq analysis reveal an activation of immune response and compromise of secretory function in major salivary glands of obese mice. Comput Struct Biotechnol J. 2023;21:105-19. DOI:10.1016/j.csbj.2022.11.054.
37. Aguirre M, Jonkers DMAE, Troost FJ, Roeselers G, Venema K. In vitro characterization of the impact of different substrates on metabolite production, energy extraction and composition of gut microbiota from lean and obese subjects. PLoS One. 2014;9:e113864. DOI:10.1371/journal.pone.0113864.
38. Kołodziej U, Maciejczyk M, Miąsko A, Matczuk J, Knaś M, Zukowski P, et al. Oxidative modification in the salivary glands of high fat-diet induced insulin resistant rats. Front Physiol. 2017;8:20. DOI:10.3389/fphys.2017.00020.
39. Stadtman ER. Protein oxidation and aging. Science. 1992;257(5074):1220-4. DOI:10.1126/science.1355616.
40. Yamamoto Y, Morozumi T, Takahashi T, Saruta J, Sakaguchi W, To M, et al. Effect of high fat and fructo-oligosaccharide consumption on immunoglobulin A in saliva and salivary glands in rats. Nutrients. 2021;13(4):1252. DOI:10.3390/nu13041252.
41. Li Y, South T, Han M, Chen J, Wang R, Huang XF. High-fat diet decreases tyrosine hydroxylase mRNA expression irrespective of obesity susceptibility in mice. Brain Res. 2009;1268:181-9. DOI: 10.1016/j.brainres.2009.02.075.
42. Solinas G, Karin M. JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction. FASEB J. 2010;24(8):2596-611. DOI: 10.1096/fj.09-151340.
43. Zalewska A, Ziembicka D, Żendzian-Piotrowska M, Maciejczyk M. The impact of high-fat diet on mitochondrial function, free radical production, and nitrosative stress in the salivary glands of Wistar rats. Oxid Med Cell Longev. 2019;2019:1-15. DOI: 10.1155/2019/2606120.
44. Tóthová L, Kamodyová N, Červenka T, Celec P. Salivary markers of oxidative stress in oral diseases. Front Cell Infect Microbiol. 2015;5:73. DOI: 10.3389/fcimb.2015.00073.
45. Chen Q, Wang Q, Zhu J, Xiao Q, Zhang L. Reactive oxygen species: key regulators in vascular health and diseases. Br J Pharmacol. 2018;175(8):1279-92. DOI: 10.1111/bph.13828.
46. Touyz RM, Briones AM. Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens Res. 2011;34(1):5-14. DOI: 10.1038/hr.2010.201.
47. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014:360438. DOI: 10.1155/2014/360438.
48. Milne GL, Yin H, Hardy KD, Davies SS, Roberts LJ. Isoprostane generation and function. Chem Rev. 2011;111(10):5973-96. DOI: 10.1021/cr200160h.
49. Milne GL, Dai Q, Roberts LJ. The isoprostanes—25 years later. Biochim Biophys Acta Mol Cell Biol Lipids. 2015;1851(4):433-45. DOI: 10.1016/j.bbalip.2014.10.007.
50. Elrayess MA, Almuraikhy S, Kafienah W, Al-Menhali A, Al-Khelaifi F, Bashah M, et al. 4-Hydroxynonenal causes impairment of human subcutaneous adipogenesis and induction of adipocyte insulin resistance. Free Radic Biol Med. 2017;104:129-37. DOI: 10.1016/j.freeradbiomed.2017.01.015.
51. Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Gerontol. 2009;44(10):625-33. DOI: 10.1016/j.exger.2009.07.003.
52. Zalewska A, Szarmach I, Żendzian-Piotrowska M, Maciejczyk M. The effect of N-acetylcysteine on respiratory enzymes, ADP/ATP ratio, glutathione metabolism, and nitrosative stress in the salivary gland mitochondria of insulin resistant rats. Nutrients. 2020;12(2):458. DOI: 10.3390/nu12020458.
53. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1-13. DOI: 10.1042/BJ20081386.
54. Nolfi-Donegan D, Braganza A, Shiva S. Mitochondrial electron transport chain: oxidative phosphorylation, oxidant production, and methods of measurement. Redox Biol. 2020;37:101674. DOI: 10.1016/j.redox.2020.101674.
55. Xiang R, Huang Y, Zhang Y, Cong X, Zhang Z, Wu L, et al. Type 2 diabetes-induced hyposalivation of the submandibular gland through PINK1/Parkin-mediated mitophagy. J Cell Physiol. 2020;235(1):232-44. DOI: 10.1002/jcp.28962.
56. Block K, Gorin Y, Abboud HE. Subcellular localization of Nox4 and regulation in diabetes. Proc Natl Acad Sci U S A. 2009;106(34):14385-90. DOI: 10.1073/pnas.0906805106.
57. Takac I, Schröder K, Zhang L, Lardy B, Anilkumar N, Lambeth JD, et al. The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem. 2011;286(15):13304-13. DOI: 10.1074/jbc.M110.192138.
58. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813-20. DOI: 10.1038/414813a.
59. Hatanaka E, Dermargos A, Hirata AE, Vinolo MAR, Carpinelli AR, Newsholme P, et al. Oleic, linoleic and linolenic acids increase ROS production by fibroblasts via NADPH oxidase activation. PLoS One. 2013;8:e58626. DOI: 10.1371/journal.pone.0058626.
60. Kadenbach B, Arnold S, Lee I, Hüttemann M. The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases. Biochim Biophys Acta. 2004;1655:400-8. DOI: 10.1016/j.bbabio.2003.06.005.
61. Zalewska A, Zięba S, Kostecka-Sochoń P, Kossakowska A, Piotrowska MZ, Matczuk J, et al. NAC supplementation of hyperglycemic rats prevents the development of insulin resistance and improves antioxidant status but only alleviates general and salivary gland oxidative stress. Oxid Med Cell Longev. 2020;2020:8831855. DOI: 10.1155/2020/8831855.
62. Melvin JE, Yule D, Shuttleworth T, Begenisich T. Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu Rev Physiol. 2005;67:445-69. DOI: 10.1146/annurev.physiol.67.041703.084745.
63. Ambudkar IS. Regulation of calcium in salivary gland secretion. Crit Rev Oral Biol Med. 2000;11(1):4-25. DOI: 10.1177/10454411000110010301.
64. Carvalho PM, Gavião MBD, Carpenter GH. Altered autophagy and sympathetic innervation in salivary glands from high-fat diet mice. Arch Oral Biol. 2017;75:107-13. DOI: 10.1016/j.archoralbio.2016.10.033.
65. Proctor GB. The physiology of salivary secretion. Periodontol 2000. 2016;70(1):11-25. DOI: 10.1111/prd.12116.
66. Hosoi K, Yao C, Hasegawa T, Yoshimura H, Akamatsu T. Dynamics of salivary gland AQP5 under normal and pathologic conditions. Int J Mol Sci. 2020;21(4):1182. DOI: 10.3390/ijms21041182.
67. Galli M, Hameed A, Żbikowski A, Zabielski P. Aquaporins in insulin resistance and diabetes: more than channels! Redox Biol. 2021;44:102027. DOI: 10.1016/j.redox.2021.102027.
68. Hurley PT, Ferguson CJ, Kwon TH, Andersen ML, Norman AG, Steward MC, et al. Expression and immunolocalization of aquaporin water channels in rat exocrine pancreas. Am J Physiol Gastrointest Liver Physiol. 2001;280(4):G701-9. DOI: 10.1152/ajpgi.2001.280.4.G701.
69. Lu Y, Chen L, Zhao B, Xiao Z, Meng T, Zhou Q, et al. Urine AQP5 is a potential novel biomarker of diabetic nephropathy. J Diabetes Complications. 2016;30(5):819-25. DOI: 10.1016/j.jdiacomp.2016.03.026.
70. Redman RS. On approaches to the functional restoration of salivary glands damaged by radiation therapy for head and neck cancer, with a review of related aspects of salivary gland morphology and development. Biotech Histochem. 2008;83(3-4):103-30. DOI: 10.1080/10520290802374683.
71. Oz HS. Nutrients, infectious and inflammatory diseases. Nutrients. 2017;9(10):1085. DOI: 10.3390/nu9101085.
72. Pişiriciler R, Çalışkan-Ak E, Emekli-Alturfan E, Yarat A, Canberk Y. Impact of experimental hyperlipidemia on histology of major salivary glands. Balkan Med J. 2009;26(4):283-91.
73. Yan MX, Li YQ, Meng M, Ren HB, Kou Y. Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia. Biochem Biophys Res Commun. 2006;347(1):192-9. DOI: 10.1016/j.bbrc.2006.06.063.
74. Jiang T, Wang Z, Proctor G, Moskowitz S, Liebman SE, Rogers T, et al. Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J Biol Chem. 2005;280(37):32317-25. DOI: 10.1074/jbc.M500801200.
75. Izumi M, Hida A, Takagi Y, Kawabe Y, Eguchi K, Nakamura T. MR imaging of the salivary glands in sicca syndrome: comparison of lipid profiles and imaging in patients with hyperlipidemia and patients with Sjögren's syndrome. AJR Am J Roentgenol. 2000;175(3):829-34. DOI: 10.2214/ajr.175.3.1750829.
76. Azevedo LR, Damante JH, Lara VS, Lauris JRP. Age-related changes in human sublingual glands: a post mortem study. Arch Oral Biol. 2005;50(6):565-74. DOI: 10.1016/j.archoralbio.2004.10.019.
77. Verma RJ, Nair A. Effect of aflatoxins on testicular steroidogenesis and amelioration by vitamin E. Food Chem Toxicol. 2002;40(5):669-72. DOI: 10.1016/S0278-6915(01)00131-4.
78. Stevens T, Conwell DL, Zuccaro G. Pathogenesis of chronic pancreatitis: an evidence-based review of past theories and recent developments. Am J Gastroenterol. 2004;99(11):2256-70. DOI: 10.1111/j.1572-0241.2004.40694.x.
79. Wilmarth PA, Riviere MA, Rustvold DL, Lauten JD, Madden TE, David LL. Two-dimensional liquid chromatography study of the human whole saliva proteome. J Proteome Res. 2004;3(5):1017-23. DOI: 10.1021/pr049911o.
80. Al-Serwi RH, El-Sherbiny M, Eladl MA, Aloyouny A, Rahman I. Protective effect of nano vitamin D against fatty degeneration in submandibular and sublingual salivary glands: a histological and ultrastructural study. Heliyon. 2021;7(4):e06932. DOI: 10.1016/j.heliyon.2021.e06932.
81. Porcheri C, Mitsiadis T. Physiology, pathology and regeneration of salivary glands. Cells. 2019;8(9):976. DOI:10.3390/cells8090976.
82. Kikuchi T, Sakaguchi W, Saruta J, Yamamoto Y, To M, Kurimoto Y, et al. Hypertriglyceridemia-induced brain-derived neurotrophic factor in rat submandibular glands. J Oral Biosci. 2020;62(4):327-35. DOI:10.1016/j.job.2020.08.003.
83. Kandeel S, Elwan WM. Effect of high-fat diet on the rat submandibular salivary glands with the possible protection by Gomisin A: light and scanning electron microscopic study. Egypt J Histol. 2023;46(2):588-602. DOI:10.21608/ejh.2022.100644.1576.
84. Matczuk J, Zalewska A, Łukaszuk B, Knaś M, Maciejczyk M, Garbowska M, et al. Insulin resistance and obesity affect lipid profile in the salivary glands. J Diabetes Res. 2016;2016:8163474. DOI:10.1155/2016/8163474.
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