Gender Specific QT Prolongation in High-Sucrose Fed Mice
PDF
Cite
Share
Request
Research Article
P: 128-136
June 2024

Gender Specific QT Prolongation in High-Sucrose Fed Mice

J Ankara Univ Fac Med 2024;77(2):128-136
No information available.
No information available
Received Date: 27.11.2023
Accepted Date: 11.06.2024
Online Date: 12.08.2024
Publish Date: 12.08.2024
PDF
Cite
Share
Request

Abstract

Objectives

The increase in insulin resistance and its impact on cardiac insulin metabolic signaling is becoming a significant contributor to heart failure, especially given the escalating rates of obesity, cardiorenal metabolic syndrome, and our aging population. Our study aims to comparatively evaluate the development of insulin resistance and the occurrence of QT lengthening depending on gender.

Materials and Methods

In our study, 8-week-old Balb/c female and male mice were used. An insulin resistant model was induced by feeding mice with standard rodent chow and tap water containing high sucrose (32%; w/v) for 14 weeks. Animals in the control groups were fed with standard rodent chow and tap water. Body weights, fasting blood glucose levels, insulin resistance using oral glucose tolerance test, food and water consumption, and electrocardiographic (ECG) parameters were measured in control and metabolic syndrome group male and female mice.

Results

The present study showed that fasting blood glucose levels were increased and insulin resistance was developed in male mice consuming 32% sucrose solution for 14 weeks, while no change was observed in female mice. According to the results, chow consumption was decreased both in male and female mice, while their body weight was not changed. Water consumption was not changed in males, while it increased in females. It was also observed that caloric intake increased significantly as a result of high-sucrose diet compared to control in both genders. No change was observed in ECG parameters of male mice, while QT was lengthened in female mice with insulin resistance, which did not show any metabolic deterioration.

Conclusion

Our results showed that no change in ECG parameters was observed in male mice with insulin resistance, while QT lengthening observed in female mice with sucrose feeding without metabolic deterioration, suggesting that female mice are more sensitive to QT lengthening induced by sugar independent of metabolic changes.

References

1
Beltrán-Sánchez H, Harhay MO, Harhay MM, et al. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. J Am Coll Cardiol. 2013;62:697-703.
2
Onat A, Can G, Yüksel H, et al., TEKHARF 2017 Tıp dünyasının kronik hastalıklara yaklaşımına öncülük. İstanbul: Logos Yayıncılık. 2017:104-19.
3
Conn PM. Animal models for the study of human disease. Academic Press. 2017.
4
Han TS, Lean ME. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease. JRSM Cardiovasc Dis. 2016;5:2048004016633371.
5
Shah SR, Park K, Alweis R. Long QT Syndrome: A Comprehensive Review of the Literature and Current Evidence. Curr Probl Cardiol. 2019;44:92-106.
6
Bazett H. An Analysis of the Time Relationships of Electrocardiograms. Annals of Noninvasive Electrocardiology. 1997;2:177-194.
7
Dahlberg P, Diamant UB, Gilljam T, et al. QT correction using Bazett’s formula remains preferable in long QT syndrome type 1 and 2. Ann Noninvasive Electrocardiol. 2021;26:e12804.
8
Syndrome NWT. Genetic and Rare Diseases Information Center (GARD)-An NCATS Program. 2022.
9
Roden DM. Long-QT Syndrome. New England Journal of Medicine. 2008;358:169-176.
10
Splawski I, Shen J, Timothy KW, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000;102:1178-1185.
11
Vink AS, Clur SB, Wilde AAM, et al. Effect of age and gender on the QTc-interval in healthy individuals and patients with long-QT syndrome. Trends Cardiovasc Med. 2018;28:64-75.
12
Schwartz PJ, Periti M, Malliani A. The long Q-T syndrome. Am Heart J. 1975;89:378-390.
13
Aromolaran AS, Boutjdir M. Cardiac Ion Channel Regulation in Obesity and the Metabolic Syndrome: Relevance to Long QT Syndrome and Atrial Fibrillation. Front Physiol. 2017;8:431.
14
Scherer PE, Hill JA. Obesity, Diabetes, and Cardiovascular Diseases: A Compendium. Circ Res. 2016;118:1703-1705.
15
Surawicz B, Parikh SR. Prevalence of male and female patterns of early ventricular repolarization in the normal ECG of males and females from childhood to old age. J Am Coll Cardiol. 2002;40:1870-1876.
16
Curtis AB, Narasimha D. Arrhythmias in women. Clin Cardiol. 2012;35:166-171.
17
Wong SK, Chin KY, Suhaimi FH, et al. Animal models of metabolic syndrome: a review. Nutr Metab (Lond). 2016;13:65.
18
Apryatin SA, Mzhel’skaya KV, Trusov NV, et al. Biochemical and Morphological Parameters of Inbred/Outbred Lines and DBCB Tetrahybrid Mouse in High-Sugar In Vivo Model of Metabolic Syndrome. Bull Exp Biol Med. 2018;166:96-101.
19
Santoso P, Amelia A, Rahayu R. Jicama (Pachyrhizus erosus) fiber prevents excessive blood glucose and body weight increase without affecting food intake in mice fed with high-sugar diet. J Adv Vet Anim Res. 2019;6:222-230.
20
King AJG Daniels, M Kennard. Animal Models of Diabetes: Methods and Protocols. 2020: Springer.
21
Jürgens H, Haass W, Castañeda TR, et al. Consuming fructose-sweetened beverages increases body adiposity in mice. Obes Res. 2005;13:1146-1156.
22
Aguilera AA, Díaz GH, Barcelata ML, et al. Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome. J Nutr Biochem. 2004;15:350-357.
23
Shahraki MR, Harati M, Shahraki AR. Prevention of high fructose-induced metabolic syndrome in male wistar rats by aqueous extract of Tamarindus indica seed. Acta Med Iran. 2011;49:277-283.
24
Spector AC, Smith JC. A detailed analysis of sucrose drinking in the rat. Physiol Behav. 1984;33:127-136.
25
Oron-Herman M, Kamari Y, Grossman E, et al. Metabolic syndrome: comparison of the two commonly used animal models. Am J Hypertens. 2008;21:1018-1022.
26
Mamikutty N, Thent ZC, Sapri SR, et al. The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. Biomed Res Int. 2014;2014:263897.
27
Sheludiakova A, Rooney K, Boakes RA. Metabolic and behavioural effects of sucrose and fructose/glucose drinks in the rat. Eur J Nutr. 2012;51:445-454.
28
Elks CM, Francis J. Central adiposity, systemic inflammation, and the metabolic syndrome. Curr Hypertens Rep. 2010;12:99-104.
29
Horton TJ, Gayles EC, Prach PA, et al. Female rats do not develop sucrose-induced insulin resistance. Am J Physiol. 1997;272:R1571-6.
30
Pettersson US, Waldén TB, Carlsson PO, et al. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One. 2012;7:e46057.
31
Nakagawa M, Ooie T, Ou B, et al. Gender differences in autonomic modulation of ventricular repolarization in humans. J Cardiovasc Electrophysiol. 2005;16:278-284.
32
Stramba-Badiale M, Spagnolo D, Bosi G, et al. Are gender differences in QTc present at birth? MISNES Investigators. Multicenter Italian Study on Neonatal Electrocardiography and Sudden Infant Death Syndrome. Am J Cardiol. 1995;75:1277-1278.
33
Sedlak T, Shufelt C, Iribarren C, Merz CN. Sex hormones and the QT interval: a review. J Womens Health (Larchmt). 2012;21:933-941.
34
Nakagawa M, Ooie T, Takahashi N, et al. Influence of menstrual cycle on QT interval dynamics. Pacing Clin Electrophysiol. 2006;29:607-613.
35
Rodriguez I, Kilborn MJ, Liu XK, et al. Drug-induced QT prolongation in women during the menstrual cycle. JAMA. 2001;285:1322-1326.
36
Saito T, Ciobotaru A, Bopassa JC, et al. Estrogen contributes to gender differences in mouse ventricular repolarization. Circ Res. 2009;105:343-352.
37
De Leo V, la Marca A, Agricola E, et al. Resting ECG is modified after oophorectomy and regresses with estrogen replacement therapy in premenopausal women. Maturitas. 2000;36:43-47.
38
Saba S, Link MS, Homoud MK, et al. Effect of low estrogen states in healthy women on dispersion of ventricular repolarization. Am J Cardiol. 2001;87:354-356
39
Singh R, Barden A, Mori T, et al. Advanced glycation end-products: a review. Diabetologia. 2001;44:129-146.
40
Semchyshyn HM, Miedzobrodzki J, Bayliak MM, et al. Fructose compared with glucose is more a potent glycoxidation agent in vitro, but not under carbohydrate-induced stress in vivo: potential role of antioxidant and antiglycation enzymes. Carbohydr Res. 2014;384:61-69.
41
Grasselli E, Baldini F, Vecchione G, et al. Excess fructose and fatty acids trigger a model of non‑alcoholic fatty liver disease progression in vitro: Protective effect of the flavonoid silybin. Int J Mol Med. 2019;44:705-712.
42
Midorikawa K, Kobayashi K, Kato S, et al. Oxidative DNA damage: Induction by fructose, in vitro, and its enhancement by hydrogen peroxide. Mutat Res Genet Toxicol Environ Mutagen. 2024;893:503719.
43
Tuncay E, Bitirim VC, Durak A, et al. Hyperglycemia-Induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release From the Sarco(endo)plasmic Reticulum and Mediate ER Stress in the Heart. Diabetes. 2017;66:1346-1358.
44
Ramirez AH, Schildcrout JS, Blakemore DL, et al. Modulators of normal electrocardiographic intervals identified in a large electronic medical record. Heart Rhythm. 2011;8:271-277.
45
Isner JM, Sours HE, Paris AL, et al. Sudden, unexpected death in avid dieters using the liquid-protein-modified-fast diet. Observations in 17 patients and the role of the prolonged QT interval. Circulation. 1979;60:1401-1412.
46
Lantigua RA, Amatruda JM, Biddle TL, et al. Cardiac arrhythmias associated with a liquid protein diet for the treatment of obesity. N Engl J Med. 1980;303:735-738.