High Fat Diet Rat Models

Abstract

Background

The prevalence of obesity is reported to be increasing owing to the high intake of dietary fat and is a predisposing risk factor with associated complex metabolic syndromes in the human population. Preclinical rodent models play a pivotal role in understanding the pathogenesis of obesity and development of new treatment strategies for humans. High-fat-diet (HFD)-induced rodents are used for chronic obesity models owing to their quick adaptation to high-fat diets and rapid body weight gain and different rats (Wistar Sprague-Dawley and Lewis) have been used by various researchers. However, the selection of appropriate stock contributes to the translation of clinically linked disease phenotypes to preclinical animal models.

Methods

The study was conducted using two commonly used rat stocks Hsd:Sprague-Dawley (SD) and Crl:Charles River (CD) to develop a chronic high-fat-diet-induced obesity model (DIO) to explore the underlying mechanisms of obesity and its utilization in drug discovery and development during preclinical stages. In addition two high-fat diets of different composition were evaluated (D12327; 40% kcal fat and D12492; 60% kcal fat) for their potential to induce obesity using these two stocks.

Results

A differential sensitivity to HFD was observed in body weight gain fat mass composition and obesity-linked symptoms such as impaired glucose tolerance insulin and leptin levels. The comparative research findings of Hsd:SD and Crl:CD rat stocks suggested that Crl:CD rats are more prone to diet-induced obesity and its associated complications.

Conclusions

Crl:CD rats were found to be a suitable model for obesity over Hsd:SD when considering the important hallmarks of metabolic disorders that may be utilized for obesity-related research.

Acknowledgments

The authors are thankful to Vikramadithyan Reeba and Nuttaki Ravikumar for their technical inputs and investigators including veterinary sciences team who have contributed during in-life phases of experiments and review of this manuscript.

1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

2. Research funding: None declared.

3. Employment or leadership: None declared.

4. Honorarium: None declared.

5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014;15:6184–223.10.3390/ijms1504618424733068 Search in Google Scholar

2. World Health Organization. Obesity and overweight fact sheet N31. Obesity facts from 2013. Available at: . Accessed 27 February, 2017. Search in Google Scholar

3. Després JP, Golay A, Sjöström L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005;353:2121–34.16291982 10.1056/NEJMoa044537 Search in Google Scholar

4. Vickers SP, Jackson HC, Cheetham SC. The utility of animal models to evaluate novel anti-obesity agents. Br J Pharmacol 2011;164:1248–62.21265828 10.1111/j.1476-5381.2011.01245.x Search in Google Scholar

5. Madsen AN, Hansen G, Paulsen SJ, Lykkegaard K, Tang-Christensen M, Hansen HS. Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome. J Endocrinol 2010;206:287–96.10.1677/JOE-10-0004 Search in Google Scholar

6. Ravinet-Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, Maffrand JP. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003;284:R345–53.12399252 10.1152/ajpregu.00545.2002 Search in Google Scholar

7. Davidson EP, Coppey LJ, Calcutt NA, Oltman CL, Yorek MA. Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction. Diab Metab Res Rev 2010;26:306–18.10.1002/dmrr.1088 Search in Google Scholar

8. Davidson EP, Coppey LJ, Dake B, Yorek MA. Effect of treatment of Sprague Dawley rats with AVE7688, enalapril, or candoxatril on diet-induced obesity. J Obes 2011;1–9. ID: 686952; PMID: 20847891. Search in Google Scholar

9. Marissal-Arvy N, Langlois A, Tridon C, Mormede P. Functional variability in corticosteroid receptors is a major component of strain differences in fat deposition and metabolic consequences of enriched diets in rat. Metab Clin Exp 2010;60:706–19.20723946 Search in Google Scholar

10. Buettner R, Scholmerich J, Bollheimer LC. High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring). 2007;15:798–808.10.1038/oby.2007.60817426312 Search in Google Scholar

11. Drake MT, Riley LK, Livingston RS. Differential susceptibility of SD and CD rats to a novel rat theilovirus. Comparative Med 2008;58:458–64. Search in Google Scholar

12. Pettersen JC, Morrissey RL, Saunders DR, Pavkov KL, Luempert LG, Turnier JC, et al. A 2-year comparison study of Crl:CD BR and Hsd:Sprague-Dawley SD rats. Fundam Appl Toxicol 1996;33:196–211.8921338 10.1006/faat.1996.0157 Search in Google Scholar

13. Brower M, Grace M, Kotz CM, Koya V. Comparative analysis of growth characteristics of Sprague Dawley rats obtained from different sources. Lab Anim Res 2015;31:166–73.26755919 10.5625/lar.2015.31.4.166 Search in Google Scholar

14. Ghibaudi L, Cook J, Farley C, Heek MV, Hwa JJ. Fat intake affects adiposity, comorbidity factors, and energy metabolism of Sprague-Dawley rats. Obes Res 2002;9:956–63. Search in Google Scholar

15. Cox JE, Sims JS. Ventromedial hypothalamic and paraventricular nucleus lesions damage a common system to produce hyperphagia. Behav Brain Res 1988;28:297–308.10.1016/0166-4328(88)90132-5 Search in Google Scholar

16. Farooqi IS, O'Rahilly S. Leptin: a pivotal regulator of human energy homeostasis. Am J Clin Nutr 2009;89:980S–4S. Search in Google Scholar

17. Woods SC, Seeley RJ, Rushing PA, D'Alessio D, Tso P. A controlled high-fat diet induces an obese syndrome in rats. J Nutr 2002;133:1082–7. Search in Google Scholar

18. Souza MV, Leite RD, Lino AD, Marqueti R, Bernardes CF, Selistre de Araújo HS, et al. Resistance training improves body composition and increases matrix metalloproteinase 2 activity in biceps and gastrocnemius muscles of diet-induced obese rats. Clinics 2014;69:265–70.10.6061/clinics/2014(04)08 Search in Google Scholar

19. Crous-Bou M, Rennert G, Salazar R, Rodriguez-Moranta F, Rennert HS, Lejbkowicz F, et al. Genetic polymorphisms in fatty acid metabolism genes and colorectal cancer. Mutagenesis 2012;27:169–76.22294764 10.1093/mutage/ger066 Search in Google Scholar

20. Marques CA, Meireles M, Norbertoa S, Leitea J, Freitasa J, Pestanaa D, et al. High-fat diet-induced obesity rat model: a comparison between Wistar and Sprague-Dawley rat. Adipocyte 2016;5:11–21.10.1080/21623945.2015.1061723 Search in Google Scholar

21. Schmiedt CW, Gogal RM, Harvey SB, Torres AK, Jarrett CL, Uh EW, et al. Biometric evidence of diet-induced obesity in Lew/Crl rats. Comparative Med 2011;61:131–7. Search in Google Scholar

22. Delarue J, LeFoll C, Corporeau C, Lucas D. N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? Reprod Nutr Dev 2004;44:289–99.10.1051/rnd:200403315460168 Search in Google Scholar

23. Heal DJ, Gosden J, Smith SL. Regulatory challenges for new drugs to treat obesity and comorbid metabolic disorders. Br J Clin Pharmacol 2009;68:861–74.20002080 10.1111/j.1365-2125.2009.03549.x Search in Google Scholar

24. Storlien LH, Higgins JA, Thomas TC, Brown MA, Wang HQ, Huang XF, et al. Diet composition and insulin action in animal models. Br J Nutr 2000;83:S85–90.10889797 Search in Google Scholar

25. Yaqoob P, Sherrington EJ, Jeffery NM, Sanderson P, Harvey DJ, Newsholme EA, et al. Comparison of the effects of a range of dietary lupon serum and tissue lipid composition in the rat. J Biochem Cell Biol 1995;27:297–310.10.1016/1357-2725(94)00065-J Search in Google Scholar

26. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rössner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005;365:1389–97.10.1016/S0140-6736(05)66374-X15836887 Search in Google Scholar

27. Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V, et al. High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 2011;57:611–24.10.1097/FJC.0b013e3181feb90a21572266 Search in Google Scholar

28. Zhuhua Z, Zhiquan W, Zhen Y, Yixin N, Weiwei Z, Xiaoyong L, et al. A novel mice model of metabolic syndrome: the high- fat-high-fructose diet-fed ICR mice. Exp Anim 2015;64, 435–42.10.1538/expanim.14-008626134356 Search in Google Scholar

29. Buettner R, Parhofer KG, Woenckhaus M, Wrede CE, Kunz-Schughart LA, Schölmerich J, et al. Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol 2006;36:485–501.10.1677/jme.1.0190916720718 Search in Google Scholar

30. Thresher JS, Podolin DA, Wei Y, Mazzeo RS, Pagliassotti MJ. Comparison of the effects of sucrose and fructose on insulin action and glucose tolerance. Am J Physiol Regul Integr Comp Physiol 2000;279:R1334–40.10.1152/ajpregu.2000.279.4.R133411004002 Search in Google Scholar

31. Ney DM, Lai HC, Lasekan JB, Lefevre M. Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats. J Nutr 1991;121:1311–22.1880609 10.1093/jn/121.9.1311 Search in Google Scholar

High Fat Diet Rat Models

Source: https://www.degruyter.com/document/doi/10.1515/jbcpp-2017-0030/html

Share this post