Isoleucine Prevents the Accumulation of Tissue Triglycerides and Upregulates the Expression of PPARα and Uncoupling Protein in Diet-Induced Obese Mice1–3

  1. Hironobu Yoshimatsu
  1. Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Yufu-Hasama, Oita, 879-5593 Japan
  1. *To whom correspondence should be addressed. E-mail: masaki{at}


In this study, we investigated the effects of the branched-chain amino acid l-isoleucine (Ile) on both obesity and glucose/fat homeostasis in mice that were fed a high-fat (45% energy) diet. The mice were divided into different treatment groups and given a high-fat diet for 6 wk. During the last 4 wk, Ile was dissolved and added to the drinking water to a final concentration of 2.5%. The control mice received vehicle alone. The mice in the Ile group had an almost 6% lower body weight gain and 49% less epididymal white adipose tissue (WAT) mass with the control group (P < 0.05). The hepatic and skeletal muscle triglyceride (TG) concentrations and degree of hyperinsulinemia in the Ile group mice were also lower than the control group by 38, 47, and 39%, respectively (P < 0.05). The WAT leptin concentration was also lower, whereas that of adiponectin was higher, in the Ile group compared with the control group (P < 0.05). The hepatic levels of protein CD36/fatty acid translocase, PPARα, and uncoupling protein (UCP) 2 and the levels of UCP3 in skeletal muscle were all greater in the Ile group than in the control mice (P < 0.05). These results demonstrate that the liver and muscle TG concentrations are both lowered by Ile treatment. In addition, the PPARα and UCP expression levels in the mouse tissues were greater in the Ile group compared with the controls. Our current data thus suggest that supplementation with Ile might be useful in the treatment of metabolic syndrome.


  • 1 Supported by Grants-in Aid from the Ministry of Education, Culture, Sports, Science and Technology, and Research Grants from the Ministry of Health, Labor and Welfare, Japan (T. Masaki and H. Yoshimatsu).

  • 2 Author disclosures: J. Nishimura, T. Masaki, M. Arakawa, M. Seike, and H. Yoshimatsu, no conflicts of interest.

  • 3 Supplemental Figure 1 is available with the online posting of this paper at

  • Manuscript received: April 16, 2009.
  • Initial review completed: May 13, 2009.
  • Revision accepted: December 23, 2009.
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