Open Access
Research (Published online: 22-11-2018)
14. Metabolic and morphometric changes in Indonesian cynomolgus monkeys (Macaca fascicularis) fed an atherogenic diet composed of locally sourced ingredients
Sri Rahmatul Laila, Dewi Apri Astuti, Irma Herawati Suparto, Ekowati Handharyani and Dondin Sajuthi
Veterinary World, 11(11): 1609-1617

Sri Rahmatul Laila: Department of Anatomy, Physiology and Pharmacology, Faculty of Veterinary Medicine, Bogor Agricultural University, Bogor, Indonesia.
Dewi Apri Astuti: Primate Research Center, Bogor Agricultural University, Bogor, Indonesia; Department of Nutrition and Feed Technology, Faculty of Animal Science, Bogor Agricultural University, Bogor, Indonesia.
Irma Herawati Suparto: Primate Research Center, Bogor Agricultural University, Bogor, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Bogor, Indonesia.
Ekowati Handharyani: Primate Research Center, Bogor Agricultural University, Bogor, Indonesia Department of Veterinary Clinic, Reproduction and Pathology, Faculty of Veterinary Medicine, Bogor Agricultural University, Bogor, Indonesia.
Dondin Sajuthi: Primate Research Center, Bogor Agricultural University, Bogor, Indonesia Department of Veterinary Clinic, Reproduction and Pathology, Faculty of Veterinary Medicine, Bogor Agricultural University, Bogor, Indonesia.

doi: 10.14202/vetworld.2018.1609-1617

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Article history: Received: 29-06-2018, Accepted: 10-10-2018, Published online: 22-11-2018

Corresponding author: Sri Rahmatul Laila


Citation: Laila SR, Astuti DA, Suparto IH, Handharyani E, Sajuthi D (2018) Metabolic and morphometric changes in Indonesian cynomolgus monkeys (Macaca fascicularis) fed an atherogenic diet composed of locally sourced ingredients, Veterinary World, 11(11): 1609-1617.

Background and Aim: This study was designed to determine the effects of a new atherogenic diet formulated at Institut Pertanian Bogor (IPB) (Bogor, Indonesia) on metabolic, morphometric, and carotid artery imaging of cynomolgus monkeys.

Materials and Methods: A total of 20 adult male cynomolgus monkeys fed IPB-1 atherogenic diet for 1 year. Total plasma cholesterol (TPC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and morphometric measurements were evaluated at baseline and monthly during the study. Carotid plaques and intima-media thickness (IMT) were measured using ultrasonography at baseline and after 8 months of treatment.

Results: This diet increased TPC, LDL, and TPC/HDL ratio and induced carotid atherosclerosis in this model. The TPC, LDL, and TPC/HDL ratio were positively associated; however, HDL was negatively associated with carotid plaques and IMT.

Conclusion: The IPB-1 atherogenic diet formulated with locally and readily available ingredients provides an economically and scientifically feasible monkey model to study atherosclerosis in Indonesia and Southeast Asia.

Keywords: atherogenic diet, carotid artery, cynomolgus, ultrasonography.


1. National Heart Lung and Blood Institute (2012) Morbidity and Mortality: 2012 Chartbook on Cardiovascular, Lung and Blood Disease. Available from: Last accessed on 27-06-2017.

2. World Health Organization (2014) Non-Communicable Disease: Country Profile 2014. World Health Organization, Geneva (CH).

3. Bloom, D.E., Chen, S., McGovern, M., Prettner, K., Candeias, V., Bernaert, A. and Cristin, S. (2015) Economics of Non-Communicable Diseases in Indonesia. Available from: Last accessed on 29-01-2018.

4. Shelton, K.A., Clarkson, T.B. and Kaplan, J.R. (2012) Nonhuman primate models of atherosclerosis. In: Abee, C.R., Mansfield, K., Tardif, S. and Moris, T., editors. Non-Human Primate In Biomedical Research. Academic Print, New York (US). [Crossref]

5. Kanthaswamy, S., Jillian, T.J.S., George, D.A., Kou, A.J., Hoffman, L.N., Doherty, T.B., Houghton, P. and Smith, D.G. (2013) The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research. J. Med. Primatol., 42(3): 120-131. [Crossref] [PubMed] [PMC]

6. Astuti, D.A., Sajuthi, D., Suparto, I.H., Kaplan, J., Appt, S. and Clarkson, TB. (2014) The development of pakans to induce atherogenic lipid profiles for cynomolgus monkeys in their country of origin. World. J. Agri. Res., 2(5): 247-251. [Crossref]

7. Clarkson, T.B., Alexander, N.J. and Morgan, T.M. (1988) Atherosclerosis of cynomolgus monkeys hyper and hyporesponsive to dietary cholesterol: Lack of effect of vasectomy. Arteriosclerosis, 8:488-498. [Crossref] [PubMed]

8. Clarkson, T.B. (1998) Nonhuman primate models of atherosclerosis. Lab. An. Sci., 48(6): 569-572. [PubMed]

9. Katan, M.B., Beynen, A.C., de Vries, J.H. and Nobels, A. (1985) The existence of consistent hypo- and hyper-responders to dietary cholesterol in man. Am. J. Epidemiol., 123(2): 221-234. [Crossref]

10. Glatz, J.F., Turner, P.R., Katan, M.B., Anton, B., Stalenhoeff, F.H. and Lewis, B. (1993) Hypo- and hyper-response of serum cholesterol level and low-density lipoprotein production and degradation to dietary cholesterol in man. Ann. N. Y. Acad. Sci., 676: 163-179. [Crossref] [PubMed]

11. Herron, K.L., Lopez, S.V., Conde, K., Ramjiganez, T., Sachter, N.S. and Fernandez, M.L. (2003) Men classified as hypo- or hyper-responders to dietary cholesterol feeding exhibit differences in lipoprotein metabolism. J. Nutr., 133(4): 1036-1042. [Crossref] [PubMed]

12. Ibanez, B., Juan, M.D., Badimon, J. and Garcia, M.J. (2009) Diagnosis of atherosclerosis by imaging. Am. J. Med., 122(1 suppl): S15-S25. [Crossref] [PubMed]

13. Molinari, F., Zeng, G. and Suri, J.S. (2010) A state of the art review on intima-media thickness (IMT) measurement and wall segmentation techniques for a carotid ultrasound. Comput. Methods Programs Biomed., 100(3): 201-221. [Crossref] [PubMed]

14. Kauffman, D., Mary, A.B., Igor, S., Eric, L.P., Smith, J., Leonard, A.R. and John, G.K. (2007) Early-Life stress and development of obesity and insulin resistance in juvenile bonnet macaques. J. Diabetes, 56(5): 1382-1386. [Crossref] [PubMed]

15. Ahmadi, S.A., Boroumand, M.A., Gohari-Moghaddam, K., Tajik, P. and Dibaj, S.M. (2008) The impact of low serum triglyceride on LDL-cholesterol estimation. Arch. Iran Med., 11(3): 318-321. [PubMed]

16. Committee on Animal Nutrition. (2003) Nutrient Requirements of Nonhuman Primates. 2nd ed. The National Academic Pr, Washington DC (US).

17. Spence, J.D. (2016) Dietary cholesterol and egg yolk should be avoided by patients at risk of vascular disease. J. Transl. Int. Med., 4(1): 20-24. [Crossref] [PubMed] [PMC]

18. Gervajio, G.C. (2005) Fatty acids and derivatives from coconut oil. In: Shahidi, F., (Ed.). Bailey's Industrial Oil and Fat Products. 6th ed. John Wiley and Sons Inc., New Jersey. [Crossref]

19. Addis, P.B., Cart, T.P., Hassel, C.A., Huang, Z.Z. and Warner, G.J. (1995) Atherogenic and anti-atherogenic factors in the human diet. Biochem. Soc. Symp., 6 (1): 259-271. [Crossref]

20. Mirzaei, H., Di Biase, S. and Longo, V.D. (2016) Dietary interventions, cardiovascular aging and disease. Animal models and human studies. Circ. Res., 118(10): 1612-1625. [Crossref]

21. Sugiri, U., Noventi, S. and Hisatome, I. (2012) Carbohydrate Diet Links To A Higher Risk Of Significant Coronary Artery Disease In Young Indonesian Patients: Cardiometabolic Investigation Study. Available from: Last accessed on 27-01-2018.

22. Aouidet, A., Bouissou, H., De La Farge, F. and Valdiguie, P. (1990) Serum reference values of the cynomolgus monkey, a model for the study of atherosclerosis. J. Clin. Chem. Clin. Biochem., 28(4): 251-252. [PubMed]

23. Register, T.C. (2009) Primate model in women's health: Inflammation and atherogenesis in female cynomolgus macaques (Macaca fascicularis). Am. J. Primatol., 71(9): 766-775. [Crossref] [PubMed] [PMC]

24. Katan, M.B. and Baynen, A.C. (1986) Characteristics of human hypo- and hyper-responders to dietary cholesterol, Am. J. Epidemiol., 125(3): 387-399. [Crossref]

25. Taher, A., Solihin, D.D., Sulistyani, S.D. and Astuti, D.A. (2016) Genetic diversity within the 3'UTR of the cynomolgus macaque (Macaca fascicularis) LDLR Gene. Int. J. Sci., 26(1): 237-248.

26. National Cholesterol Education Program. (2002) Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (adult treatment panel III). Circulation, 106(25): 3143-3421. [Crossref] [PubMed]

27. Hao, W. and Friedman, A. (2014) The LDL-HDL profile determines the risk of atherosclerosis: A mathematical model. PLoS One, 9(3): e90497. [Crossref]

28. Toth, P.P., Barter, P.J., Rosenson, R.S., Boden, W.E., Chapman, M.J., Cuchel, M., D'Agostino, R.B., Davidson, M.H., Davidson, W.S., Heinecke, J.W., Karas, R.H., Kontush, A., Krauss, R.M., Miller, M. and Rader, D.J. (2013) High-density lipoproteins: A consensus statement from the national lipid association. J. Clin. Lipid., 7(5): 484-525. [Crossref] [PubMed]

29. Clarkson, T.B., Ethun, K.F., Chen, H., Golden, D., Floyd, E. and Appt, S.E. (2013) Effect of bezedoxifene alone and with conjugated equine estrogens on coronary and peripheral atherosclerosis in postmenopausal monkeys. Menopause, 20(3): 274-281. [PubMed] [PMC]

30. Lutz, C.K., Coleman, K., Worlein, J.M., Kroeker, R., Menard, M.T., Rosenberg, K., Meyer, J.S. and Novak, M.A. (2016) Factors influencing alopecia and hair cortisol in rhesus macaques (Macaca mulatta). J. Med. Primatol., 5(4): 180-188. [Crossref] [PubMed] [PMC]

31. Tang, R., Hennig, M. and Thomasson, B. (2000) Baseline reproducibility of B-mode ultrasonic measurement of carotid artery intima-media thickness: The European lacidipine study on atherosclerosis (ELSA). J. Hypertens., 18(2): 197-201. [Crossref]

32. Zeng, W., Wen, X., Gong, L., Sun, J., Yang, J., Liao, J., Qian, C., Chen, W., Song, B. and Gao, F. (2015) Establishment and ultrasound characteristics of atherosclerosis in rhesus monkeys. BME, 14(1): S13. [Crossref]

33. Finn, A.V., Kolodgie, F.D. and Virmani, R. (2010) Correlation between carotid intimal/medial thickness and atherosclerosis: A point of view from pathology. Arterioscler. Thromb. Vasc. Biol., 30(2): 177-181. [Crossref] [PubMed]

34. Baldassarre, D., Amato, M., Bondioli, A., Sirtori, C.R. and Tremoli, E. (2000) Carotid artery intima-media thickness measured by ultrasonography in normal clinical practice correlates well with atherosclerosis risk factors. Stroke, 31(10): 2426-2430. [Crossref]

35. Yang, C., Sun, Z., Li, Y., Ai, J., Sun, Q. and Tian, Y. (2014) The correlation between serum lipid profile with carotid intima-media thickness and plaque. BMC Cardiovasc. Disord., 14: 181-186. [Crossref] [PubMed] [PMC]

36. Tamada, M., Makita, S., Abiko, A., Naganuma, Y., Nagai, M. and Nakamura, M. (2010) Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio as a useful marker for early-stage carotid atherosclerosis. Metab. Clin. Exp., 59(5): 653-657. [Crossref] [PubMed]

37. Inaba, Y., Chen, J.A. and Bergmann, S.R. (2012) Carotid plaque, compared with carotid intima-media thickness, more accurately predict coronary artery disease events: A meta-analysis. Atherosclerosis, 220(1): 128-133. [Crossref] [PubMed]

38. Stein, J.H., Korcarz, C.E., Hurst, R.T., Lonn, E., Kendall, C.B., Mohler, E.R., Najjar, S.S., Rembold, C.M. and Post, W.S. (2008) Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force. J. Am. Soc. Echocardiogr., 21(2): 93-111. [Crossref] [PubMed]

39. Chen, Y., Xiong, H., Wu, D., Phirbulal, S., Tian, X., Zhang, R., Lu, M., Wu, W. and Huang, W. (2015) Relationship of short-term blood pressure variability with carotid intima-media thickness in hypertensive patients. Biomed. Eng. Online, 14: 71-85. [Crossref] [PubMed] [PMC]