Decreased peroxisome proliferator–activated receptor α gene expression is associated with dyslipidemia in a rat model of chronic renal failure

Mori, Yusaku; Hirano, Tsutomu; Nagashima, Masaharu; Shiraishi, Yuji; Fukui, Tetsuya; Adachi, Mitsuru

doi:10.1016/j.metabol.2007.07.016

Cited by 26 publications

(19 citation statements)

References 32 publications

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“…First, the Niemann-Pick C1-like 1 (NPC1L1) gene is reported to be downregulated by the activation of PPARα by its agonists, such as WY14643, eicosapentaenoic acid and docosahexaenoic acid 25) . Since the PPARα gene expression is decreased 26) and the n-3 polyunsaturated fatty acid profile is unfavorably altered 27) in patients with renal failure, intestinal cholesterol absorption via NPC1L1 could be increased in subjects with a decreased renal function. Second, in the presence of increased cholesterol absorption, the delivery of cholesterol of chylomicron remnants to the liver would be increased, resulting in suppressed de novo synthesis of cholesterol by the liver, although we found an insignificant correlation between the lathosterol and campesterol concentrations.…”

Section: Discussionmentioning

confidence: 99%

Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus

Sonoda

Shoji

Kimoto³

et al. 2014

JAT

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Aim: Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD. Methods: The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD. Results: The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) μg/mL and 2.3 (1.7-3.0) μg/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables. Conclusions: The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.

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Section: Discussionmentioning

confidence: 99%

Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus

Sonoda

Shoji

Kimoto³

et al. 2014

JAT

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“…In fact the downregulation of several genes, along with the changes in the composition of lipoprotein particles and the direct inhibitory effect of various uremic 'toxins' on the enzymes involved in lipid metabolism, represents the most important pathophysiological mechanisms underlying the development of hypertriglyceridemia in renal failure [7] .…”

Section: Vldl and Triglyceride Levelsmentioning

confidence: 99%

Alterations of Lipid Metabolism in Chronic Nephropathies: Mechanisms, Diagnosis and Treatment

Lacquaniti

Bolignano

Donato

et al. 2010

Kidney Blood Press Res

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Nephropathic subjects show an increased tendency to develop cardiovascular diseases, mainly as the consequence of several risk factors including increased oxidative stress, inflammation, physical inactivity, anemia, vascular calcification, and endothelial dysfunction. The alterations in lipid metabolism represent a relatively lesser important cause of genesis and progression of atherosclerosis. Unfortunately, in these patients the atherogenic potential of dyslipidemia may depend more on apolipoproteins than on lipid abnormalities, and may not always be recognized by measurement of plasma lipids alone. The aim of this review was therefore to analyze the main lipid alterations that can occur in nephropathic patients, as well as their causes and their effects on the cardiovascular system. The clinical evidence and recommendations for the use of lipid-regulating drugs in patients with chronic kidney disease, nephrotic syndrome, in patients undergoing hemo- and peritoneal dialysis and in transplanted patients was also reviewed. Moreover, we analyzed the link between dyslipidemia and kidney disease onset and progression and the role of statins in preventing it.

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“…Experimental studies revealed that the accumulation of triglyceride-rich lipoproteins (very-low-density lipoprotein (VLDL), chylomicrons and their remnants) in individuals with predialysis CKD is mainly due to their decreased catabolism [20]. The downregulation of the expression of several genes [21,22,23] along with the changes in the composition of lipoprotein particles [24] and the direct inhibitory effect of various uremic ‘toxins’ on the enzymes involved in lipid metabolism [25], represent the most important pathophysiological mechanisms underlying the development of hypertriglyceridemia in renal failure. Interestingly, it has been proposed that secondary hyperparathyroidism may also contribute to the impaired catabolism of triglyceride-rich lipoproteins [26, 27] and that parathyroidectomy or the administration of the calcium channel blocker verapamil [28] may partially ameliorate the hypertriglyceridemia of CKD.…”

Section: Lipids In Ckd Stages 1–4mentioning

confidence: 99%

Dyslipidemia in Chronic Kidney Disease: An Approach to Pathogenesis and Treatment

Tsimihodimos

Dounousi

Siamopoulos³

2008

Am J Nephrol

123

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Decreased peroxisome proliferator–activated receptor α gene expression is associated with dyslipidemia in a rat model of chronic renal failure

Cited by 26 publications

References 32 publications

Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus

Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus

Alterations of Lipid Metabolism in Chronic Nephropathies: Mechanisms, Diagnosis and Treatment

Dyslipidemia in Chronic Kidney Disease: An Approach to Pathogenesis and Treatment

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