Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Joanna Niewiadomska
 -- 1308 2022-04-27 15:59:27 |
2 format correct
Conner Chen
 + 5 word(s) 1313 2022-04-28 05:21:50 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Niewiadomska, J. Animal Model of Diabetes: Zucker Diabetic Fatty Rats. Encyclopedia. Available online: https://encyclopedia.pub/entry/22388 (accessed on 30 December 2024).
Niewiadomska J. Animal Model of Diabetes: Zucker Diabetic Fatty Rats. Encyclopedia. Available at: https://encyclopedia.pub/entry/22388. Accessed December 30, 2024.
Niewiadomska, Joanna. "Animal Model of Diabetes: Zucker Diabetic Fatty Rats" Encyclopedia, https://encyclopedia.pub/entry/22388 (accessed December 30, 2024).
Niewiadomska, J. (2022, April 27). Animal Model of Diabetes: Zucker Diabetic Fatty Rats. In Encyclopedia. https://encyclopedia.pub/entry/22388
Niewiadomska, Joanna. "Animal Model of Diabetes: Zucker Diabetic Fatty Rats." Encyclopedia. Web. 27 April, 2022.
Animal Model of Diabetes: Zucker Diabetic Fatty Rats
Edit

Laboratory Zucker Diabetic Fatty (ZDF) rat are derived from the Zucker Fatty strain. A spontaneous mutation that occurred in Zucker Fatty (ZF) rats resulted in a diabetic phenotype. The inbreeding of ZF rats carrying the desired mutation led to the development of a new strain called the Zucker Diabetic Fatty strain. The polyphenolic compounds analyzed in studies conducted using this animal model include pomegranate extracts and cocoa flavonols.

laboratory animal models

1. Introduction

Metabolic syndrome (MetS), a risk factor for cardiovascular diseases (CVD) and type 2 diabetes, affects a significant part of the population worldwide, with a prevalence of 10–30%. It is a clustering of interrelated metabolic disorders, which include insulin [1][2][3][4][5][6] resistance, central obesity, hypertriglyceridemia, lowered HDL cholesterol concentration, and hypertension [1][2]. MetS has had different criteria over the years, mainly associated with distinguishable definitions of abdominal obesity, with the World Health Organization (WHO), the National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP111), the American Association of Clinical Endocrinologists (AACE), and the European Group for Study of Insulin Resistance (EGSIR) all proposing their own diagnostic criteria [3][4]. Finally, in 2005, the International Diabetes Federation (IDF) provided a standardized consensus. The proposed definition includes waist circumference as a precondition for the identification of MetS and embraces the standard features of the previous definition, such as the assessment of triglyceride (TG) level, high-density lipoprotein cholesterol (HDL), blood pressure, and fasting glucose [5][6].
Metabolic pathways comprising the pathomechanism of MetS have not yet been clearly characterized. However, this is a tedious process due to the wide range of different pathophysiological mechanisms needing to be considered. Evidence suggests that various factors may predispose one to the development of MetS, such as genetics, diet, lifestyle, and gut microbiome [7][8]. A syndrome, which is more of a clinical term than a disease entity, suggests an association with other disorders. The current research shows that MetS predisposes one to cardiovascular dysfunctions via, e.g., atherosclerotic changes [9][10][11] and type 2 diabetes [12]. The correlation with other disorders is based on oxidative stress’s role in the pathomechanism. Studies have indicated that there may be an association between MetS and Parkinson’s disease [13], obstructive sleep apnea [14], and the progression and development of different cancers, such as colon cancer or gastric cancer [15][16][17]. Treatment is mainly based on lifestyle changes involving increased physical activity and a balanced diet. Researchers are currently looking for new substances that could significantly mitigate the severity and progression of MetS symptoms by affecting the metabolic pathways involved in the MetS pathophysiology. Numerous studies based on animal models have demonstrated the existence of a relationship between the intake of polyphenol-rich products and the mitigation of individual components of MetS. A beneficial effect was obtained via a reduction in body weight, blood pressure, blood glucose levels, and improved lipid metabolism.

2. Animal Model of Diabetes: Zucker Diabetic Fatty (ZDF) Rats

Laboratory ZDF rats are derived from the Zucker Fatty strain. A spontaneous mutation that occurred in ZF rats resulted in a diabetic phenotype. The inbreeding of ZF rats carrying the desired mutation led to the development of a new strain called the Zucker Diabetic Fatty strain. The cause of the genetic defect leading to impaired beta-cell function is not clear. However, a number of changes in the expression of pancreatic islet genes have been described, including a reduced expression of the GLUT2 transporter and increased activity of glucokinase and hexokinase. ZDF rats have higher insulin resistance and are less obese compared with the parental strain [18]. Male ZDF rats develop diabetes at eight weeks of age, which is associated with changes in the morphology of pancreatic islets. Female rats do not develop overt diabetes, despite their significant level of insulin resistance, except when they are fed a high-fat diet [19]. In male ZDF rats, diabetes-related cataract is observed at 15 weeks of age, first as angiogenesis changes at the periphery of the lens, which progress to the development of a mature cataract at 21 weeks of age [20][21]. Laboratory ZDF rats provide, in particular, a suitable animal model of type 1 and type 2 diabetes and its complications, including retinopathy, cardiomyopathy, and diabetic nephropathy. In addition, due to its specificity (hyperglycemia, hyperinsulinemia, impaired glucose metabolism), the strain can be used in studies on MetS [22].
The polyphenolic compounds analyzed in studies conducted using this animal model include pomegranate extracts and cocoa flavonols.

2.1. Pomegranate

The pomegranate (Punica granathum L.) is a long-lived plant that belongs to the Lythraceae family. Its various parts are rich sources of a variety of compounds. Pomegranate seed oil contains punicinic acid (a polyunsaturated fatty acid) and phytoestrogens. The juice and peel are rich in numerous polyphenolic compounds, especially tannins and flavonoids. Pomegranate tannins include ellagitannins, such as punicalagin and punicalin, whereas pomegranate flavonoids include, in particular, anthocyanins and flavonols. Moreover, pomegranate juice and peel contain numerous catechins. In turn, pomegranate bark and roots are sources of alkaloids, including pelletierine and isopelletierine, which are used in folk medicine as anthelmintics. Pomegranate polyphenols have antioxidant properties, as they indirectly inhibit inflammatory markers. They also present anti-carcinogenic effects [23][24]. Pomegranate extracts seem to have a beneficial effect on changes characteristic of MetS, as confirmed by the findings from the available studies. ZDF rats treated with pomegranate flower extract (500 mg/kg, p.o. × six weeks) had milder symptoms of diabetes- and obesity-related hepatic steatosis (lower liver weight, lower triglyceride levels, and lower lipid droplet content) compared with controls. This was due, at least in part, to the enhanced expression of genes associated with the oxidation of fatty acids, including peroxisome proliferator-activated receptors (PPAR-α), acyl-CoA oxidase, and carnitine palmitoyltransferase-1 [25]. A 6-week treatment with pomegranate extract (500 mg/kg p.o.) was also found to reduce the collagen deposit area in the left ventricle as well as the perivascular collagen deposit areas. The reduction in cardiac fibrosis was mediated by the modulation of the endothelin-1 (ET-1) and nuclear factor kappa B (NF-κB) pathways. The diminished cardiac fibrosis was accompanied by reduced hyperglycemia and hyperlipidemia [26]. In another study on ZDF rats with insulin resistance and hyperlipidemia, Punica granathum extract reduced cardiac triglyceride accumulation and decreased circulating triglyceride and cholesterol levels. In that study, the improvement in cardiac lipid metabolism was mediated by the activation of, e.g., PPAR-alpha [27].

2.2. Cocoa

The cocoa tree (Theobroma cacao L.) is a tree in the family Malvaceae native to the forests of South and Central America. Its seeds, commonly known as cocoa, are used in many food products. The chemical composition of cocoa includes numerous polyphenolic compounds, including proanthocyanins, catechins, flavan-3-ols, and anthocyanins. It is currently being investigated whether it may play a significant role as a dietary intervention to reduce cardiovascular risk in type 2 diabetes, given that it reduces plasma lipid levels and promotes the production of nitric oxide (NO) [28]. Recent studies have shown that cocoa polyphenols also have beneficial effects on carbohydrate metabolism. In one study, male ZDF rats fed a cocoa powder-rich diet (10%) for ten weeks showed improved glucose tolerance and insulin resistance. Moreover, the consumption of a diet rich in cocoa products had protective effects against diabetes-induced structural alterations in the kidneys. The antihyperglycemic effects of cocoa, protecting against diabetic nephropathy, were mediated through the inhibition of the synthesis of gluconeogenic enzymes, i.e., phosphoenolpyruvate-carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase), and glucose transporters (i.e., sodium-glucose-co-transporter-2 (SGLT-2) and glucose-transporter-2 (GLUT-2)) in the renal cortex [29]. In both in vivo (ZDF rats) and in vitro (HepG2 cells) models, cocoa flavonols, especially (−)-epicatechin, improved lipid metabolism by reducing body weight gain and lipid accumulation in liver cells [30]. Cocoa intake also improves the gut microbiota via interactions that may contribute to its antidiabetic effect. Male ZDF rats fed with 10% cocoa presented more acetate-producing bacteria and had a reduced amount of lactate-producing bacteria compared to the lean group. The modified gut microbiota was associated with an improvement in glucose homeostasis and intestinal integrity and with a reduced expression of pro-inflammatory cytokines, such as tumor necrosis factor-a (TNF-a) or interleukin-6 (IL-6), in the colon of rats [31].
This entry is adapted from 10.3390/biology11040559

References

  1. Saklayen, M.G. The Global Epidemic of the Metabolic Syndrome. Curr. Hypertens. Rep. 2018, 20, 12.
  2. McCracken, E.; Monaghan, M.; Sreenivasan, S. Pathophysiology of the metabolic syndrome. Clin. Dermatol. 2018, 36, 14–20.
  3. Alberti, K.G.M.M.; Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z.; Cleeman, J.I.; Donato, K.A.; Fruchart, J.-C.; James, W.P.T.; Loria, C.M.; Smith, S.C., Jr. Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation 2009, 120, 1640–1645.
  4. Alberti, K.G.M.M.; Zimmet, P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet. Med. 1998, 15, 539–553.
  5. Alberti, K.G.M.M.; Zimmet, P.; Shaw, J. Metabolic syndrome—A new world-wide definition. A consensus statement from the international diabetes federation. Diabet. Med. 2006, 23, 469–480.
  6. Wen, J.; Yang, J.; Shi, Y.; Liang, Y.; Wang, F.; Duan, X.; Lu, X.; Tao, Q.; Lu, X.; Tian, Y.; et al. Comparisons of different metabolic syndrome definitions and associations with coronary heart disease, stroke, and peripheral arterial disease in a rural Chinese population. PLoS ONE 2015, 10, e0126832.
  7. Wang, H.H.; Lee, D.K.; Liu, M.; Portincasa, P.; Wang, D.Q.-H. Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome. Pediatr. Gastroenterol. Hepatol. Nutr. 2020, 23, 189–230.
  8. Dabke, K.; Hendrick, G.; Devkota, S. The gut microbiome and metabolic syndrome. J. Clin. Investig. 2019, 129, 4050–4057.
  9. Penman, K. Does Metabolic Syndrome Increase Cardiovascular Risk? Ph.D. Thesis, Auckland University of Technology, Auckland, New Zealand, 2011.
  10. Tune, J.D.; Goodwill, A.G.; Sassoon, D.J.; Mather, K.J. Cardiovascular consequences of metabolic syndrome. Transl. Res. 2017, 183, 57–70.
  11. Cao, H.-L.; Chen, X.-B.; Lu, J.-G.; Hou, Z.-H.; Fang, X.; Gao, Y.; Yu, F.-F. Metabolic syndrome and coronary artery calcification: A community-based natural population study. Chin. Med. J. 2013, 126, 4618–4623.
  12. Marjani, A. Metabolic syndrome and diabetes: A review. J. Clin. Basic Res. 2017, 1, 36–43.
  13. Zhang, P.; Tian, B. Metabolic syndrome: An important risk factor for Parkinson’s disease. Oxidative Med. Cell. Longev. 2014, 2014, 729194.
  14. Kostoglou-Athanassiou, I.; Athanassiou, P. Metabolic syndrome and sleep apnea. Hippokratia 2008, 12, 81.
  15. Russo, A.; Autelitano, M.; Bisanti, L. Metabolic syndrome and cancer risk. Eur. J. Cancer 2008, 44, 293–297.
  16. Braun, S.; Bitton-Worms, K.; LeRoith, D. The link between the metabolic syndrome and cancer. Int. J. Biol. Sci. 2011, 7, 1003.
  17. Metere, A.; Giacomell, L. Absorption, metabolism and protective role of fruits and vegetables polyphenols against gastric cancer. Eur. Rev. Med. Pharmacol. Sci. 2017, 21, 5850–5858.
  18. Conn, P.M. Animal Models for the Study of Human Disease; Academic Press: Lubbock, TX, USA, 2017.
  19. Melmed, S.; Polonsky, K.S.; Larsen, P.R.; Kronenberg, H.M. Williams Textbook of Endocrinology E-Book; Elsevier Health Sciences: Philadelphia, PA, USA, 2015.
  20. Kowluru, R.A.; Mishra, M.; Kowluru, A.; Kumar, B. Hyperlipidemia and the development of diabetic retinopathy: Comparison between type 1 and type 2 animal models. Metabolism 2016, 65, 1570–1581.
  21. Szabó, K.; Énzsöly, A.; Dékány, B.; Szabó, A.; Hajdú, R.I.; Radovits, T.; Mátyás, C.; Oláh, A.; Laurik, L.L.; Somfai, G.M.; et al. Histological Evaluation of Diabetic Neurodegeneration in the Retina of Zucker Diabetic Fatty (ZDF) Rats. Sci. Rep. 2017, 7, 8891.
  22. Wong, S.K.; Chin, K.-Y.; Suhaimi, F.H.; Fairus, A.; Ima-Nirwana, S. Animal models of metabolic syndrome: A review. Nutr. Metab. 2016, 13, 65.
  23. Zarfeshany, A.; Asgary, S.; Javanmard, S.H. Potent health effects of pomegranate. Adv. Biomed. Res. 2014, 3, 100.
  24. Johanningsmeier, S.D.; Harris, G.K. Pomegranate as a functional food and nutraceutical source. Annu. Rev. Food Sci. Technol. 2011, 2, 181–201.
  25. Xu, K.Z.-Y.; Zhu, C.; Kim, M.S.; Yamahara, J.; Li, Y. Pomegranate flower ameliorates fatty liver in an animal model of type 2 diabetes and obesity. J. Ethnopharmacol. 2009, 123, 280–287.
  26. Huang, T.H.W.; Yang, Q.; Harada, M.; Li, G.Q.; Yamahara, J.; Roufogalis, B.D.; Li, Y. Pomegranate Flower Extract Diminishes Cardiac Fibrosis in Zucker Diabetic Fatty Rats: Modulation of Cardiac Endothelin-1 and Nuclear Factor-kappaB Pathways. J. Cardiovasc. Pharmacol. 2005, 46, 856–862.
  27. Huang, T.H.W.; Peng, G.; Kota, B.P.; Li, G.Q.; Yamahara, J.; Roufogalis, B.D.; Li, Y. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: Role of lowering circulating lipids. Br. J. Pharmacol. 2005, 145, 767–774.
  28. Campia, U.; Panza, J.A. Flavanol-rich cocoa: A promising new dietary intervention to reduce cardiovascular risk in type 2 diabetes? J. Am. Coll. Cardiol. 2008, 51, 2150–2152.
  29. Álvarez-Cilleros, D.; López-Oliva, E.; Goya, L.; Martín, M.Á.; Ramos, S. Cocoa intake attenuates renal injury in Zucker Diabetic fatty rats by improving glucose homeostasis. Food Chem. Toxicol. 2019, 127, 101–109.
  30. Cordero-Herrera, I.; Martin, M.A.; Fernández-Millán, E.; Álvarez, C.; Goya, L.; Ramos, S. Cocoa and cocoa flavanol epicatechin improve hepatic lipid metabolism in in vivo and in vitro models. Role of PKCζ. J. Funct. Foods 2015, 17, 761–773.
  31. Álvarez-Cilleros, D.; Ramos, S.; López-Oliva, M.E.; Escrivá, F.; Álvarez, C.; Fernández-Millán, E.; Martín, M.Á. Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats. Food Res. Int. 2020, 132, 109058.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Endocrinology & Metabolism
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Joanna Niewiadomska
View Times: 409
Revisions: 2 times (View History)
Update Date: 28 Apr 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback