Skip to main content
SpringerLink
Log in

Consumption of combined fructose and sucrose diet exacerbates oxidative stress, hypertrophy and CaMKIIδ oxidation in hearts from rats with metabolic syndrome

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The prevalence of the metabolic syndrome (MetS) and its cardiac comorbidities as cardiac hypertrophy (CH) have increased considerably due to the high consumption of carbohydrates, such as sucrose and/or fructose. We compared the effects of sucrose (S), fructose (F) and their combination (S + F) on the development of MetS in weaned male Wistar rats and established the relationship between the consumption of these sugars and the degree of cardiac CH development, oxidative stress (OS) and Calcium/calmodulin-dependent protein kinase type II subunit delta oxidation (ox-CaMKIIδ). 12 weeks after the beginning of treatments with S, F or S + F, arterial pressure was measured and 8 weeks later (to complete 20 weeks) the animals were sacrificed and blood samples, visceral adipose tissue and hearts were obtained. Biochemical parameters were determined in serum and cardiac tissue to evaluate the development of MetS and OS. To evaluate CH, atrial natriuretic peptide (ANP), CaMKIIδ and ox-CaMKIIδ were determined by western blot and histological studies were performed in cardiac tissue. Our data showed that chronic consumption of S + F exacerbates MetS-induced CH which is related with a higher OS and ox-CaMKIIδ.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

source of reactive oxygen species causing oxidative stress in different organs such as the heart. B CaMKIIδ activation is carried out by Ca2+-CaM complex binding to the regulatory domain, however, when this binding is reversed CaMKIIδ is autoinhibited. However, Ca2+-CaM complex-independent activation also occurs. Oxidation at the regulatory site of methionine 281 and 282 is a type of Ca2+-CaM-independent activation of this enzyme, moreover, it is dependent on the production of reactive oxygen species and a state of oxidative stress. This activation is known as pathological activation because it leads to the development of different abnormal conditions such as cardiac hypertrophy

Similar content being viewed by others

Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

References

  1. Pepin A, Stanhope KL, Imbeault P (2019) Are fruit juices healthier than sugar-sweetened beverages? A review. Nutrients 11(5):1–16. https://doi.org/10.3390/nu11051006

    Article  CAS  Google Scholar 

  2. Ng SW, Slining MM, Popkin BM (2012) Use of Caloric and Noncaloric Sweeteners in US Consumer Packaged Foods, 2005–2009. J Acad Nutr Diet 12(11):1828-1834.e6. https://doi.org/10.1016/j.jand.2012.07.009

    Article  Google Scholar 

  3. Balderas-Villalobos J, Molina-Muñoz T, Mailloux-Salinas P, Bravo G, Carvajal K, Gómez-Viquez NL (2013) Oxidative stress in cardiomyocytes contributes to decreased SERCA2a activity in rats with metabolic syndrome. Am J Physiol 305(9):H1344–H1353. https://doi.org/10.1152/ajpheart.00211.2013

    Article  CAS  Google Scholar 

  4. Feillet-Coudray C, Fouret G, Vigor C, Bonafos B, Jover B, Blachnio-Zabielska A et al (2019) Long-term measures of dyslipidemia, inflammation, and oxidative stress in rats fed a high-fat/high-fructose diet. Lipids 54(1):81–97. https://doi.org/10.1002/lipd.12128

    Article  CAS  PubMed  Google Scholar 

  5. Szűcs G, Sója A, Péter M, Sárközy M, Bruszel B, Siska A et al (2019) Prediabetes induced by fructose-enriched diet influences cardiac lipidome and proteome and leads to deterioration of cardiac function prior to the development of excessive oxidative stress and cell damage. Hindawi Oxidat Med Cell Longev 2019:3218275. https://doi.org/10.1155/2019/3218275

    Article  CAS  Google Scholar 

  6. Zhang YB, Meng YH, Chang S, Zhang RY, Shi C (2016) High fructose causes cardiac hypertrophy via mitochondrial signaling pathway. Am J Transl Res 8(11):4869–4880

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Kitagawa A, Ohta Y, Ohashi K, Yashiro K, Fukuzawa K (2020) Effect of high fructose-induced metabolic syndrome on tissue vitamin e and lipid peroxide levels in rats. J Nutr Sci Vitaminol. https://doi.org/10.3177/jnsv.66.200

    Article  PubMed  Google Scholar 

  8. Moreno-Fernández S, Garcés-Rimón M, Vera G, Astier J, Landrier JF, Miguel M (2018) High fat/high glucose diet induces metabolic syndrome in an experimental rat model. Nutrients. https://doi.org/10.3390/nu10101502

    Article  PubMed  PubMed Central  Google Scholar 

  9. Vona R, Gambardella L, Cittadini C, Straface E, Pietraforte D (2019) Biomarkers of oxidative stress in metabolic syndrome and associated diseases. Oxid Med Cell Longev 2019:8267234. https://doi.org/10.1155/2019/8267234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Aydin S, Aksoy A, Aydin S, Kalayci M, Yilmaz M, Kuloglu T et al (2014) Today’s and yesterday’s of pathophysiology: biochemistry of metabolic syndrome and animal models. Nutrition 30(1):1–9. https://doi.org/10.1016/j.nut.2013.05.013

    Article  CAS  PubMed  Google Scholar 

  11. Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K et al (2013) Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation. Nature. https://doi.org/10.1038/nature12537

    Article  PubMed  PubMed Central  Google Scholar 

  12. Erickson JR, Joiner M, Ling A, Guan X, Kutschke W, Yang J, Oddis CV et al (2008) A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell. https://doi.org/10.1016/j.cell.2008.02.048

    Article  PubMed  PubMed Central  Google Scholar 

  13. Erickson JR, Julie He B, Grumbach IM, Anderson ME (2011) CaMKII in the cardiovascular system: sensing redox states. Physiol Rev 91(3):889–915. https://doi.org/10.1152/physrev.00018.2010

    Article  CAS  PubMed  Google Scholar 

  14. Feng N, Anderson ME (2017) CaMKII is a nodal signal for multiple programmed cell death pathways in heart. J Mol Cell Cardiol 103:102–109. https://doi.org/10.1016/j.yjmcc.2016.12.007

    Article  CAS  PubMed  Google Scholar 

  15. Qu J, Mei Q, Niu R (2019) Oxidative CaMKII as a potential target for inflammatory disease (Review). Mol Med Rep 20(2):863–870. https://doi.org/10.3892/mmr.2019.10309

    Article  CAS  PubMed  Google Scholar 

  16. Zhong P, Quan D, Peng J, Xiong X, Liu Y, Kong B et al (2017) Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo. J Mol Cell Cardiol 109:1–16. https://doi.org/10.1016/j.yjmcc.2017.06.010

    Article  CAS  PubMed  Google Scholar 

  17. Mattiazzi A, Bassani RA, Escobar AL, Palomeque J, Valverde CA, Vila Petroff M et al (2015) Chasing cardiac physiology and pathology down the CaMKII cascade. Am J Physiol 308(10):H1177–H1191. https://doi.org/10.1152/ajpheart.00007.2015

    Article  CAS  Google Scholar 

  18. Federico M, Portiansky EL, Sommese L, Alvarado FJ, Blanco PG, Zanuzzi CN et al (2017) Calcium-calmodulin-dependent protein kinase mediates the intracellular signalling pathways of cardiac apoptosis in mice with impaired glucose tolerance. J Physiol. https://doi.org/10.1113/JP273714

    Article  PubMed  PubMed Central  Google Scholar 

  19. Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65(4):1220S-1228S. https://doi.org/10.1093/ajcn/65.4.1220s

    Article  CAS  PubMed  Google Scholar 

  20. Colado-Velázquez J, Mailloux-Salinas P, Medina-Contreras J, Cruz-Robles D, Bravo G (2015) Effect of Serenoa Repens on oxidative stress, inflammatory and growth factors in obese Wistar rats with benign prostatic hyperplasia. Phyther Res 29(10):1525–1531. https://doi.org/10.1002/ptr.5406

    Article  Google Scholar 

  21. Carvajal K, El Hafidi M, Marin-Hernández A, Moreno-Sánchez R (2005) Structural and functional changes in heart mitochondria from sucrose-fed hypertriglyceridemic rats. Biochim Biophys Acta. https://doi.org/10.1016/j.bbabio.2005.08.001

    Article  PubMed  Google Scholar 

  22. El Hafidi M, Cuéllar A, Ramírez J, Baos G (2001) Effect of sucrose addition to drinking water, that induces hypertension in the rats, on liver microsomal Δ9 and Δ5-desaturase activities. J Nutr Biochem 12:396–403. https://doi.org/10.1016/S0955-2863(01)00154-1

    Article  PubMed  Google Scholar 

  23. Fuente-Martín E, García-Cáceres C, Granado M, Sánchez-Garrido MA, Tena-Sempere M, Frago LM et al (2012) Early postnatal overnutrition increases adipose tissue accrual in response to a sucrose-enriched diet. Am J Physiol. https://doi.org/10.1152/ajpendo.00618.2011

    Article  Google Scholar 

  24. Kim M, Do GY, Kim I (2020) Activation of the renin-angiotensin system in high fructose-induced metabolic syndrome. Korean J Physiol Pharmacol. https://doi.org/10.4196/KJPP.2020.24.4.319

    Article  PubMed  PubMed Central  Google Scholar 

  25. Johnson RJ, Segal MS, Sautin Y, Nakagawa T, Feig DI, Kang DH et al (2007) Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr 86(4):899–906

    CAS  PubMed  Google Scholar 

  26. Baños G, Medina-Campos ON, Maldonado PD, Zamora J, Pérez I, Pavón N et al (2005) Activities of antioxidant enzymes in two stages of pathology development in sucrose-fed rats. Can J Physiol Pharmacol. https://doi.org/10.1139/y05-013

    Article  PubMed  Google Scholar 

  27. McEniery CM, Yasmin WS, Maki-Petaja K, McDonnell B, Sharman JE et al (2005) Increased stroke volume and aortic stiffness contribute to isolated systolic hypertension in young adults. Hypertension. https://doi.org/10.1161/01.HYP.0000165310.84801.e0

    Article  PubMed  Google Scholar 

  28. Souza Cruz EM, Bitencourt de Morais JM, Dalto da Rosa CV, da Silva SM, Comar JF, de Almeida Chuffa LG et al (2020) Long-term sucrose solution consumption causes metabolic alterations and affects hepatic oxidative stress in Wistar rats. Biol Open 9(3):bio047282. https://doi.org/10.1242/bio.047282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sulzbacher Da Silva B, Macedo A, Paulino B, Taffarel M, Borba IG, Ortega Telles L et al (2021) High sucrose diet attenuates oxidative stress, inflammation and liver injury in thioacetamide-induced liver cirrhosis. Life Sci 267:118944. https://doi.org/10.1016/j.lfs.2020.118944

    Article  CAS  Google Scholar 

  30. Gantner BN, LaFond KM, Bonini MG (2020) Nitric oxide in cellular adaptation and disease. Redox Biol 34:101550. https://doi.org/10.1016/j.redox.2020.101550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang C-H, Pandey S, Sivalingam K, Asokan Shibu M, Kuo W-W, Padma Viswanadha V et al (2021) Leech extract: a candidate cardioprotective against hypertension-induced cardiac hypertrophy and fibrosis. J Ethnopharmacol 264:113346. https://doi.org/10.1016/j.jep.2020.113346

    Article  CAS  PubMed  Google Scholar 

  32. Brady TM (2016) The role of obesity in the development of left ventricular hypertrophy among children and adolescents. Curr Hypertens Rep 18(1):3. https://doi.org/10.1007/s11906-015-0608-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cerrudo CS, Cavallero S, Fermepin MR, González GE, Donato M, Kouyoumdzian NM et al (2021) Cardiac natriuretic peptide profiles in chronic hypertension by single or sequentially combined renovascular and DOCA-salt treatments. Front Physiol 12:651246. https://doi.org/10.3389/fphys.2021.651246

    Article  PubMed  PubMed Central  Google Scholar 

  34. Shimizu I, Minamino T (2016) Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol 97:245–262. https://doi.org/10.1016/j.yjmcc.2016.06.001

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The research was supported by CONACYT Post-graduate Fellowship No. 456311.

Funding

Funding was provided by Consejo Nacional de Ciencia y Tecnología (456311).

Author information

Authors and Affiliations

  1. Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional, Col. Granjas Coapa, Calz. de los Tenorios 235, 14330, Mexico City, Mexico

    David Julian Arias-Chávez, Patrick Mailloux-Salinas, Norma Leticia Gómez-Viquez & Guadalupe Bravo

  2. Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico

    Julio Altamirano

  3. Laboratorio de Farmacología y Toxicología, Hospital Infantil de México Federico Gómez (HIMFG), Mexico City, Mexico

    Fengyang Huang

Authors
  1. David Julian Arias-Chávez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Mailloux-Salinas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julio Altamirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fengyang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Norma Leticia Gómez-Viquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guadalupe Bravo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GB and NLGV contributed to the study design. DJAC, PMS conceived experiments and analyzed data. DJAC and JA contributed to helpful discussion and FH reviewed the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Norma Leticia Gómez-Viquez or Guadalupe Bravo.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arias-Chávez, D.J., Mailloux-Salinas, P., Altamirano, J. et al. Consumption of combined fructose and sucrose diet exacerbates oxidative stress, hypertrophy and CaMKIIδ oxidation in hearts from rats with metabolic syndrome. Mol Cell Biochem 477, 1309–1320 (2022). https://doi.org/10.1007/s11010-022-04364-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-022-04364-w

Keywords

Search

Navigation