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High-fat diet combined with low-dose streptozotocin injections induces metabolic syndrome in Macaca mulatta

Endocrine volume 49, pages 659–668 (2015)Cite this article

Abstract

Metabolic syndrome (MetS) is associated with abdominal obesity, hyperlipidemia, insulin resistance, and type 2 diabetes mellitus, and increases the risk of cardiovascular disease. Given the complex multifactorial pathogenesis of MetS, qualified animal models are currently seriously limited for researchers. The aim of our study was to develop a MetS model in juvenile rhesus monkeys (Macaca mulatta). Rhesus monkeys (1-year-old) fed a high-fat diet (15 % fat, 2 % cholesterol) were used as the HF group (n = 6), and those on a normal diet (5 % fat) were used as the control group (n = 4). After being fed a high-fat diet for approximately 12 months, 2 monkeys (HF + STZ group) were injected with low-dose streptozotocin (STZ, 25 mg/kg) twice, with a 7 days interval, and were then fed the same diet continuously for another 24 months. After 36 months of treatment, the high-fat diet monkeys, including the HF and HF + STZ groups, had acquired increased body weights, abnormal serum lipids, and impaired glucose tolerance compared to the control group. In addition, much more marked metabolic changes were observed in the two monkeys of the HF + STZ group, particularly in terms of high-blood glucose level and insulin resistance. Morphological observation of biopsies of liver and pancreatic tissues showed decreased islet number and mass and decreased insulin staining in the monkeys of the HF + STZ group. In addition, Oil red O staining suggested remarkable accumulation of lipid droplets in the hepatocytes. Our study suggested that a long-term high-fat diet followed with a low-dose STZ was able to induce MetS in juvenile rhesus monkeys with faster pathophysiological progress compared with high-fat diet induction alone. Our primary data showed that this method may have potentials to develop MetS animal model in non-human primates.

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Acknowledgments

This study was supported by the National Program for High Technology Research and Development of China (No. 2012AA020702), the Program of National Natural Science Foundation of China (81000351), and the National Key Clinical Project.

Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, this paper.

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Affiliations

  1. Key Laboratory of Transplant Engineering and Immunology, NHFPC, Regenerative Medicine Research Center, West China Hospital, Sichuan University, No. 1, Ke yuan 4th Road, Gao Peng Street, Chengdu, 610041, Sichuan, People’s Republic of China

    Linzhao Li, Yanrong Lu, Jingping Liu, Lan Li, Chengshi Wang, Li Li, Jingqiu Cheng & Younan Chen

  2. Animal Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Guangneng Liao & Guang Yang

  3. Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Xiaojiong Du

  4. Department of Endocrine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Yan Ren

  5. National Center for Safety Evaluation of Traditional Chinese Medicine, Chengdu, People’s Republic of China

    Zhihui Zhong

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  1. Linzhao Li
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  2. Guangneng Liao
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  3. Guang Yang
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  4. Yanrong Lu
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  5. Xiaojiong Du
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  7. Lan Li
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  9. Li Li
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  10. Yan Ren
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  11. Zhihui Zhong
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Correspondence to Jingqiu Cheng or Younan Chen.

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Li, L., Liao, G., Yang, G. et al. High-fat diet combined with low-dose streptozotocin injections induces metabolic syndrome in Macaca mulatta . Endocrine 49, 659–668 (2015). https://doi.org/10.1007/s12020-015-0542-9

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  • DOI: https://doi.org/10.1007/s12020-015-0542-9

Keywords

  • Metabolic syndrome
  • Rhesus monkey
  • Low-dose streptozotocin
  • High-fat diet
  • Insulin resistance