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.
Highlights
Metabolic syndrome, which is characterized by concurrent existence of obesity, dyslipidemia, hyperinsulinemia, hyperglycemia, and hypertension, is increasingly common because of increased prevalence of obesity
PPAR-␥ϩ/ϩ mice on an high-fat diet (HFD) were significantly heavier than PPAR-␥ϩ/ϩ mice on a low-fat diet (LFD)
PPAR-␥ϩ/Ϫ mice were significantly protected against obesity, insulin resistance, and the altered adipokine secretions during the 16-wk HFD, no differences in food intake were observed between PPAR-␥ϩ/ϩ and PPAR-␥ϩ/Ϫ mice (Table 1, Figure 1, A and B)
Summary
Metabolic syndrome, which is characterized by concurrent existence of obesity, dyslipidemia, hyperinsulinemia, hyperglycemia, and hypertension, is increasingly common because of increased prevalence of obesity. This syndrome is a growing health problem because of the associated increased risk for cardiovascular disease and premature death.[1,2] a recent report suggested that individuals with metabolic syndrome are at increased risk for developing chronic kidney diseases (CKD).[3]. We investigated how favorable systemic metabolic conditions under an HFD can affect renal lipid metabolism and renal injury by using heterozygous peroxisome proliferator– activated receptor-␥– deficient (PPAR-␥ϩ/Ϫ) mice, which were previously reported to be protected against HFD-induced obesity and insulin resistance
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