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International Journal of Molecular Medicine
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December 2013 Volume 32 Issue 6

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Article

Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice

  • Authors:
    • Dal Kim
    • Jung Eun Lee
    • Yu Jin Jung
    • Ae Sin Lee
    • Sik Lee
    • Sung Kwang Park
    • Suhn Hee Kim
    • Byung-Hyun Park
    • Won Kim
    • Kyung Pyo Kang
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Research Institute of Clinical Medicine and Diabetes Research Center, Chonbuk National University Medical School, Deokjin-gu, Jeonju 561-712, Republic of Korea, Department of Physiology and Diabetes, Chonbuk National University Medical School, Deokjin-gu, Jeonju 561-712, Republic of Korea, Department of Biochemistry and Diabetes Research Center, Chonbuk National University Medical School, Deokjin-gu, Jeonju 561-712, Republic of Korea
  • Pages: 1293-1302
    |
    Published online on: September 25, 2013
       https://doi.org/10.3892/ijmm.2013.1508
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Abstract

Metabolic syndrome is characterized by insulin resistance, dyslipidemia and hypertension. These metabolic changes contribute to the development of obesity-induced kidney injury. AMP-activated protein kinase (AMPK) is a ubiquitous enzyme that is involved in the cellular metabolic response to metabolic stress. Metformin, an AMPK activator, has been reported to exert a protective effect against non-alcoholic steatohepatitis. However, little is known about its role in the pathogenesis of obesity-induced renal injury. The aim of this study was to investigate the effects of metformin on high-fat diet (HFD)-induced kidney injury. Obesity was induced by HFD (60% of total calories from fat, 20% protein and 20% carbohydrates) in 6-week-old C57BL/6 mice. Mice were fed HFD plus 0.5% metformin. The effects of metformin on HFD-induced renal injury were evaluated by determining metabolic parameters, serum adipokine levels and renal AMPK/acetyl-CoA carboxylase (ACC) activities, as well as a histological examination. HFD induced metabolic derangement, systemic insulin resistance and glomerular mesangial matrix expansion. The administration of metformin reduced HFD-induced metabolic derangement and renal injury. The administration of metformin reduced the HFD-induced increase in adipokine expression and macrophage infiltration. Moreover, renal AMPK activity, which was decreased by HFD, was recovered following the administration of metformin; in addition, fatty acid oxidation was increased by the inhibition of ACC. These results indicate that metformin exerts beneficial effects on obesity-induced renal injury by regulating systemic inflammation, insulin resistance and the renal AMPK/ACC pathway. The clinical application of metformin to obese or early diabetic patients may be helpful in preventing obesity- or diabetes-related kidney disease.
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Copy and paste a formatted citation
Spandidos Publications style
Kim D, Lee JE, Jung YJ, Lee AS, Lee S, Park SK, Kim SH, Park B, Kim W, Kang KP, Kang KP, et al: Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice. Int J Mol Med 32: 1293-1302, 2013.
APA
Kim, D., Lee, J.E., Jung, Y.J., Lee, A.S., Lee, S., Park, S.K. ... Kang, K.P. (2013). Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice. International Journal of Molecular Medicine, 32, 1293-1302. https://doi.org/10.3892/ijmm.2013.1508
MLA
Kim, D., Lee, J. E., Jung, Y. J., Lee, A. S., Lee, S., Park, S. K., Kim, S. H., Park, B., Kim, W., Kang, K. P."Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice". International Journal of Molecular Medicine 32.6 (2013): 1293-1302.
Chicago
Kim, D., Lee, J. E., Jung, Y. J., Lee, A. S., Lee, S., Park, S. K., Kim, S. H., Park, B., Kim, W., Kang, K. P."Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice". International Journal of Molecular Medicine 32, no. 6 (2013): 1293-1302. https://doi.org/10.3892/ijmm.2013.1508
Copy and paste a formatted citation
x
Spandidos Publications style
Kim D, Lee JE, Jung YJ, Lee AS, Lee S, Park SK, Kim SH, Park B, Kim W, Kang KP, Kang KP, et al: Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice. Int J Mol Med 32: 1293-1302, 2013.
APA
Kim, D., Lee, J.E., Jung, Y.J., Lee, A.S., Lee, S., Park, S.K. ... Kang, K.P. (2013). Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice. International Journal of Molecular Medicine, 32, 1293-1302. https://doi.org/10.3892/ijmm.2013.1508
MLA
Kim, D., Lee, J. E., Jung, Y. J., Lee, A. S., Lee, S., Park, S. K., Kim, S. H., Park, B., Kim, W., Kang, K. P."Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice". International Journal of Molecular Medicine 32.6 (2013): 1293-1302.
Chicago
Kim, D., Lee, J. E., Jung, Y. J., Lee, A. S., Lee, S., Park, S. K., Kim, S. H., Park, B., Kim, W., Kang, K. P."Metformin decreases high-fat diet-induced renal injury by regulating the expression of adipokines and the renal AMP-activated protein kinase/acetyl-CoA carboxylase pathway in mice". International Journal of Molecular Medicine 32, no. 6 (2013): 1293-1302. https://doi.org/10.3892/ijmm.2013.1508
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