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Role of Altered Renal Lipid Metabolism in the Development of Renal Injury Induced by a High-Fat Diet

Shinji Kume^*, Takashi Uzu^*, Shin-ichi Araki^*, Toshiro Sugimoto^*, Keiji Isshiki^*, Masami Chin-Kanasaki^*, Masayoshi Sakaguchi^*, Naoto Kubota, Yasuo Terauchi, Takashi Kadowaki, Masakazu Haneda, Atsunori Kashiwagi^* and Daisuke Koya^*,||

^* Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Second Department of Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, and ^|| Division of Endocrinology & Metabolism, Kanazawa Medical University, Kahoku-Gun, Ishikawa, Japan

Correspondence: Dr. Daisuke Koya, Division of Endocrinology & Metabolism, Kanazawa Medical University, Kahoku-Gun, Ishikawa 920-0293, Japan. Phone: +81-76-286-2211; Fax: +81-76-286-6927; E-mail: koya0516{at}kanazawa-med.ac.jp

Received for publication January 23, 2007. Accepted for publication June 7, 2007.

Metabolic syndrome is associated with increased risk of chronic kidney disease, and the renal injury in patients with metabolic syndrome may be a result of altered renal lipid metabolism. We fed wild-type or insulin-sensitive heterozygous peroxisome proliferator–activated receptor –deficient (PPAR^+/–) mice a high-fat diet for 16 weeks. In wild-type mice, this diet induced core features of metabolic syndrome, subsequent renal lipid accumulation, and renal injury including glomerulosclerosis, interstitial fibrosis, and albuminuria. Renal lipogenesis accelerated, determined by increased renal mRNA expression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase (ACC) and by increased ACC activity. In addition, renal lipolysis was suppressed, determined by reduced mRNA expression of the lipolytic enzyme carnitine palmitoyl acyl-CoA transferase 1 and by reduced activity of AMP-activated protein kinase. In PPAR^+/– mice, renal injury, systemic metabolic abnormalities, renal accumulation of lipids, and the changes in renal lipid metabolism were attenuated. Thus, a high-fat diet leads to an altered balance between renal lipogenesis and lipolysis, subsequent renal accumulation of lipid, and renal injury. We suggest that renal lipid metabolism could serve as a new therapeutic target to prevent chronic kidney disease in patients with metabolic syndrome.

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				N. Deji, S. Kume, S.-i. Araki, M. Soumura, T. Sugimoto, K. Isshiki, M. Chin-Kanasaki, M. Sakaguchi, D. Koya, M. Haneda, et al. Structural and functional changes in the kidneys of high-fat diet-induced obese mice Am J Physiol Renal Physiol, January 1, 2009; 296(1): F118 - F126. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673