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.

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.

• 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
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 32 Issue 6 Pg. 1293-302 (Dec 2013) ISSN: 1791-244X [Electronic] Greece
• PMID: 24068196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adipokines
• Transforming Growth Factor beta1
• Metformin
• AMP-Activated Protein Kinases
• Acetyl-CoA Carboxylase

Topics

• AMP-Activated Protein Kinases (metabolism)
• Acetyl-CoA Carboxylase (metabolism)
• Adipokines (blood, metabolism)
• Animals
• Diet, High-Fat
• Glucose Intolerance (blood, drug therapy, enzymology, pathology)
• Inflammation (pathology)
• Insulin Resistance
• Kidney (drug effects, enzymology, pathology)
• Kidney Tubules (drug effects, metabolism, pathology)
• Male
• Metformin (pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Oxidation-Reduction (drug effects)
• Podocytes (drug effects, metabolism, pathology)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (metabolism)