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

  • Published online on: Wednesday, September 25, 2013
  • Pages: 1293-1302
  • DOI: 10.3892/ijmm.2013.1508

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.
Journal Cover

December 2013
Volume 32 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

2012 Impact Factor: 1.957
Ranked #26/121 Medicine Research and Experimental
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Kim, D., Lee, J., Jung, Y., Lee, A., Lee, S., Park, S., Kim, S., Park, B., Kim, W., & Kang, K. (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(6), 1293-1302.
MLA
Kim, Lee, Jung, Lee, Lee, Park, Kim, Park, Kim, and Kyung Kang. "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 International Journal of Molecular Medicine 32.6 (2013): 1293-1302.
Chicago
Kim, Lee, Jung, Lee, Lee, Park, Kim, Park, Kim, and Kyung Kang. "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 International Journal of Molecular Medicine 32 no. 6 (2013): 1293-1302.