title: Role of altered renal lipid metabolism in the development of renal injury induced by a high-fat diet.
abstract: 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 gamma-deficient (PPARgamma(+/-)) 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 PPARgamma(+/-) 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.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Araki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Isshiki
authors.forename: Masami
authors.initials: M
authors.lastname: Chin-Kanasaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D024821:Metabolic Syndrome / Q000150:complications*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics
chemical_list: D004041:Dietary Fats; D047495:PPAR gamma