Volume 29, Issue 3 (September 2025)                   Physiol Pharmacol 2025, 29(3): 284-292 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Karbaschi R, Salimi M, Zardooz H. Pancreatic HB9 protein expression is affected by long-term high-fat diet in female rat dams. Physiol Pharmacol 2025; 29 (3) : 6
URL: http://ppj.phypha.ir/article-1-2361-en.html
Abstract:   (1314 Views)

Introduction: Maternal high-fat feeding has been identified as a risk factor for metabolic disorders involving abnormal glucose homeostasis and reduced whole-body insulin sensitivity. Recognizing factors like HB9, which play a role in the development of pancreatic β-cells and the release of insulin, is crucial for preventing disruptions in glucose metabolism.
Methods: Twenty female Wistar rats were randomly divided into normal (N) and high-fat (HF) groups, each receiving their specific diets during the pre-pregnancy, pregnancy, and lactation periods (10 weeks). At the end of lactation, the animals’ body weight, food consumption, and calorie intake were measured. Additionally, fasting plasma levels of glucose, insulin, and corticosterone were assessed, and the homeostatic model assessment of β-cell function (HOMA-β) was calculated. Pancreatic tissue was collected to evaluate HB9 protein levels, while the adrenal glands were separated and weighed.
Results:
The HF group showed significant increases in adrenal gland weight, plasma corticosterone levels, and pancreatic HB9 protein expression compared to the N group. Despite this, there were no significant variations in plasma glucose and insulin concentrations, HOMA-β index, or body weight among the study groups. Whereas, the HF group consumed less food.
Conclusion: Chronic intake of high-fat foods can act as a psychophysical stressor, triggering the hypothalamic-pituitary-adrenal (HPA) axis and resulting in elevated plasma corticosterone levels in female rat dams. This rise in corticosterone may lead to an upsurge in HB9 protein expression, potentially preventing disturbances in glucose regulation.

Article number: 6
Full-Text [PDF 564 kb]   (76 Downloads)    

References
1. Acosta-Montaño P, García-González V. Effects of dietary fatty acids in pancreatic beta cell metabolism, implications in homeostasis. Nutrients 2018; 10: 393. [DOI:10.3390/nu10040393]
2. Ans A H, Anjum I, Satija V, Inayat A, Asghar Z, Akram I, et al. Neurohormonal regulation of appetite and its relationship with stress: A mini literature review. Cureus 2018; 10. [DOI:10.7759/cureus.3032]
3. Armoni M, Harel C, Bar-Yoseph F, Milo S, Karnieli E. Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. Journal of Biological Chemistry 2005; 280: 34786-34795. [DOI:10.1074/jbc.M502740200]
4. Barnett A, Martino E, Knibbs L D, Shaw J E, Dunstan D W, Magliano D J, et al. The neighbourhood environment and profiles of the metabolic syndrome. Environ Health 2022; 21: 1-18. [DOI:10.1186/s12940-022-00894-4]
5. Beaudry J L, Riddell M C. Effects of glucocorticoids and exercise on pancreatic β-cell function and diabetes development. Diabetes/metabolism research and reviews 2012; 28: 560-573. [DOI:10.1002/dmrr.2310]
6. Benite-Ribeiro S A, Santos J M, Duarte J A R. Does high fat diet have the stress-like effect on animals? Diabetes & Clinical Diagnosis. 2015. [DOI:10.15344/2394-1499/2015/112]
7. Bhandari U, Kumar V, Khanna N, Panda B P. The effect of high-fat diet-induced obesity on cardiovascular toxicity in Wistar albino rats. Hum Exp Toxicol 2011; 30: 1313-1321. [DOI:10.1177/0960327110389499]
8. Busceti C L, Ferese R, Bucci D, Ryskalin L, Gambardella S, Madonna M, et al. Corticosterone upregulates gene and protein expression of catecholamine markers in organotypic brainstem cultures. Int J Mol Sci 2019; 20: 2901. [DOI:10.3390/ijms20122901]
9. de Moura e Dias M, Dos Reis S A, da Conceição L L, Sediyama C M N d O, Pereira S S, de Oliveira L L, et al. Diet-induced obesity in animal models: points to consider and influence on metabolic markers. Diabetol Metab Syndr 2021; 13: 1-14. [DOI:10.1186/s13098-021-00647-2]
10. Desai M, Jellyman J K, Han G, Beall M, Lane R H, Ross M G. Maternal obesity and high-fat diet program offspring metabolic syndrome. Am J Obstet Gynecol 2014; 211: 237. e1-237. e13. [DOI:10.1016/j.ajog.2014.03.025]
11. Elsakr J M, Zhao S K, Ricciardi V, Dean T A, Takahashi D L, Sullivan E, et al. Western-style diet consumption impairs maternal insulin sensitivity and glucose metabolism during pregnancy in a Japanese macaque model. Scientific Reports 2021; 11: 12977. [DOI:10.1038/s41598-021-92464-w]
12. Fenichel P. Lifestyle and environmental factors in metabolic diseases; endocrine disruptors: new diabetogens? 19th European Congress of Endocrinology 2017; 49. [DOI:10.1530/endoabs.49.S21.1]
13. Fine N H, Doig C L, Elhassan Y S, Vierra N C, Marchetti P, Bugliani M, et al. Glucocorticoids reprogram β-cell signaling to preserve insulin secretion. Diabetes 2018; 67: 278-290. [DOI:10.2337/db16-1356]
14. Gawlińska K, Gawliński D, Filip M, Przegaliński E. Relationship of maternal high-fat diet during pregnancy and lactation to offspring health. Nutrition Reviews 2021; 79: 709-725. [DOI:10.1093/nutrit/nuaa020]
15. Gosadi I M . Assessment of the environmental and genetic factors influencing prevalence of metabolic syndrome in Saudi Arabia. Saudi Med J 2016; 37: 12. [DOI:10.15537/smj.2016.1.12675]
16. Harrison K A, Thaler J, Pfaff S L, Gu H, Kehrl J H. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet 1999a; 23: 71-75. [DOI:10.1038/12674]
17. Harrison K A, Thaler J, Pfaff S L, Gu H, Kehrl J H. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet 1999b; 23: 71-75. [DOI:10.1038/12674]
18. Higa T S, Spinola A V, Fonseca-Alaniz M H, Sant F, Evangelista A. Comparison between cafeteria and high-fat diets in the induction of metabolic dysfunction in mice. International journal of physiology, pathophysiology and pharmacology 2014; 6: 47.
19. Izadi M S, Eskandari F, Binayi F, Salimi M, Rashidi F S, Hedayati M, et al. Oxidative and endoplasmic reticulum stress develop adverse metabolic effects due to the high-fat high-fructose diet consumption from birth to young adulthood. Life Sci 2022; 309: 120924. [DOI:10.1016/j.lfs.2022.120924]
20. Janssen J A J. New insights into the role of insulin and hypothalamic-pituitary-adrenal (hpa) axis in the metabolic syndrome. Int J Mol Sci 2022; 23: 8178. [DOI:10.3390/ijms23158178]
21. Ji F, Ning F, Duan H, Kaprio J, Zhang D, Zhang D, et al. Genetic and environmental influences on cardiovascular disease risk factors: a study of Chinese twin children and adolescents. Twin Research and Human Genetics 2014; 17: 72-79. [DOI:10.1017/thg.2014.5]
22. Kaneto H, Matsuoka T-a. Role of pancreatic transcription factors in maintenance of mature β-cell function. Int J Mol Sci 2015; 16: 6281-6297. [DOI:10.3390/ijms16036281]
23. Khalil W J, Akeblersane M, Khan A S, Moin A S M, Butler A E J. Environmental pollution and the risk of developing metabolic disorders: Obesity and diabetes. Int J Mol Sci 2023; 24: 8870. [DOI:10.3390/ijms24108870]
24. Kruger N J. The Bradford method for protein quantitation. The protein protocols handbook 2009: 17-24. [DOI:10.1007/978-1-59745-198-7_4]
25. Lam T K, Carpentier A, Lewis G F, van de Werve G, Fantus I G, Giacca A. Mechanisms of the free fatty acid-induced increase in hepatic glucose production. Am J Physiol Endocrinol Metab 2003; 284: E863-E873. [DOI:10.1152/ajpendo.00033.2003]
26. Lambillotte C, Gilon P, Henquin J-C. Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets. J Clin Invest 1997; 99: 414-423. [DOI:10.1172/JCI119175]
27. Lasker S, Rahman M M, Parvez F, Zamila M, Miah P, Nahar K, et al. High-fat diet-induced metabolic syndrome and oxidative stress in obese rats are ameliorated by yogurt supplementation. Scientific Reports 2019; 9: 20026. [DOI:10.1038/s41598-019-56538-0]
28. Leotta C G, Federico C, Brundo M V, Tosi S, Saccone S. HLXB9 gene expression, and nuclear location during in vitro neuronal differentiation in the SK-N-BE neuroblastoma cell line. PLoS One 2014; 9: e105481. [DOI:10.1371/journal.pone.0105481]
29. Li S-W, Yu H-R, Sheen J-M, Tiao M-M, Tain Y-L, Lin I-C, et al. A maternal high-fat diet during pregnancy and lactation, in addition to a postnatal high-fat diet, leads to metabolic syndrome with spatial learning and memory deficits: beneficial effects of resveratrol. Oncotarget 2017; 8: 111998. [DOI:10.18632/oncotarget.22960]
30. Manti M, Fornes R, Qi X, Folmerz E, Lindén Hirschberg A, de Castro Barbosa T, et al. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring. The FASEB Journal 2018; 32: 4158-4171. [DOI:10.1096/fj.201701263RR]
31. Marques C, Meireles M, Norberto S, Leite J, Freitas J, Pestana D, et al. High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat. Adipocyte 2016; 5: 11-21. [DOI:10.1080/21623945.2015.1061723]
32. Mendes-da-Silva C, Giriko C Á, Mennitti L V, Hosoume L F, Souto T d S, Silva A V d. Maternal high-fat diet during pregnancy or lactation changes the somatic and neurological development of the offspring. Arquivos de neuro-psiquiatria 2014; 72: 136-144. [DOI:10.1590/0004-282X20130220]
33. Mosser R E, Maulis M F, Moullé V S, Dunn J C, Carboneau B A, Arasi K, et al. High-fat diet-induced β-cell proliferation occurs prior to insulin resistance in C57Bl/6J male mice. Am J Physiol Endocrinol Metab 2015; 308: E573-E582. [DOI:10.1152/ajpendo.00460.2014]
34. Namvar S, Gyte A, Denn M, Leighton B, Piggins H D, Integrative, Physiology C. Dietary fat and corticosterone levels are contributing factors to meal anticipation. Am J Physiol Regul Integr Comp Physiol 2016; 310: R711-R723. [DOI:10.1152/ajpregu.00308.2015]
35. O’Dowd J F, Stocker C J. Endocrine pancreatic development: impact of obesity and diet. Front Physiol 2013; 4: 170. [DOI:10.3389/fphys.2013.00170]
36. Oh Y S, Bae G D, Baek D J, Park E-Y, Jun H-S. Fatty acid-induced lipotoxicity in pancreatic beta-cells during development of type 2 diabetes. Frontiers in endocrinology 2018; 9: 384. [DOI:10.3389/fendo.2018.00384]
37. Paula A B R, de Coutinho Miranda D, Nogueira F T, de Lauro Castrucci A M, Isoldi M C. Does a high-fat diet affect the circadian clock, or is it the other way around? A systematic review. Nutrition Research 2020; 84: 1-13. [DOI:10.1016/j.nutres.2020.10.003]
38. Roat R, Rao V, Doliba N M, Matschinsky F M, Tobias J W, Garcia E, et al. Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57BL/6J mice. PLoS One 2014; 9: e86815. [DOI:10.1371/journal.pone.0086815]
39. Sadeghimahalli F, Karbaschi R, Salimi M, Khodagholi F, Zardooz H J. Biochemistry. Pancreatic HB9 protein level is affected by early life stress in young adult rats: possible involvement of TNF-α and corticosterone. Arch Physiol Biochem 2021; 127: 406-413. [DOI:10.1080/13813455.2019.1645699]
40. Saengnipanthkul S, Noh H L, Friedline R H, Suk S, Choi S, Acosta N K, et al. Maternal exposure to high-fat diet during pregnancy and lactation predisposes normal weight offspring mice to develop hepatic inflammation and insulin resistance. Physiological Reports 2021; 9: e14811. [DOI:10.14814/phy2.14811]
41. Sahoo K, Sahoo B, Choudhury A K, Sofi N Y, Kumar R, Bhadoria A S. Childhood obesity: causes and consequences. J Family Med Prim Care 2015; 4: 187. [DOI:10.4103/2249-4863.154628]
42. Satokar V V, Vickers M H, Reynolds C M, Ponnampalam A P, Firth E C, Garg M L, et al. Fish oil supplementation of rats fed a high fat diet during pregnancy improves offspring insulin sensitivity. Front Nutr 2022; 9: 968443. [DOI:10.3389/fnut.2022.968443]
43. Sharma R B, Alonso L C. Lipotoxicity in the pancreatic beta cell: not just survival and function, but proliferation as well? Current diabetes reports 2014; 14: 1-9. [DOI:10.1007/s11892-014-0492-2]
44. Shi K, Parekh V I, Roy S, Desai S S, Agarwal S K. The embryonic transcription factor Hlxb9 is a menin interacting partner that controls pancreatic β-cell proliferation and the expression of insulin regulators. Endocr Relat Cancer 2013; 20: 111. [DOI:10.1530/ERC-12-0077]
45. Sullivan E L, Nousen E K, Chamlou K A, Grove K L. The impact of maternal high-fat diet consumption on neural development and behavior of offspring. International journal of obesity supplements 2012; 2: S7-S13. [DOI:10.1038/ijosup.2012.15]
46. Teeple K, Rajput P, Gonzalez M, Han-Hallett Y, Fernández-Juricic E, Casey T. High fat diet induces obesity, alters eating pattern and disrupts corticosterone circadian rhythms in female ICR mice. PLoS One 2023; 18: e0279209. [DOI:10.1371/journal.pone.0279209]
47. Udagawa H, Funahashi N, Nishimura W, Uebanso T, Kawaguchi M, Asahi R, et al. Glucocorticoid receptor-NECAB1 axis can negatively regulate insulin secretion in pancreatic β-cells. Scientific Reports 2023; 13: 17958. [DOI:10.1038/s41598-023-44324-y]
48. von Frankenberg A D, Marina A, Song X, Callahan H S, Kratz M, Utzschneider K M. A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults. Eur J Nutr 2017; 56: 431-443. [DOI:10.1007/s00394-015-1108-6]
49. Wali J A, Jarzebska N, Raubenheimer D, Simpson S J, Rodionov R N, O’Sullivan J F. Cardio-metabolic effects of high-fat diets and their underlying mechanisms-A narrative review. Nutrients 2020; 12: 1505. [DOI:10.3390/nu12051505]
50. Wali J A, Ni D, Facey H J, Dodgson T, Pulpitel T J, Senior A M, et al. Determining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice. Nat Commun 2023; 14: 4409. [DOI:10.1038/s41467-023-40039-w]
51. Wang L, Xu F, Song Z, Han D, Zhang J, Chen L, et al. A high fat diet with a high C18: 0/C16: 0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice. Lipids Health Dis 2020; 19: 1-13. [DOI:10.1186/s12944-020-01346-z]
52. Ye R, Onodera T, Scherer P E. Lipotoxicity and β cell maintenance in obesity and type 2 diabetes. J Endocr Soc 2019; 3: 617-631. [DOI:10.1210/js.2018-00372]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.