Dataset Information

Loss of Renal Tubular PGC-1? Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

ABSTRACT: The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1? is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1? in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1? seems largely dispensable for basal renal physiology. However, the role of PGC-1? in renal mitochondrial biogenesis indicates that activation of PGC-1? in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction.

SUBMITTER: Svensson K

PROVIDER: S-EPMC4963111 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

Svensson Kristoffer K Schnyder Svenia S Cardel Bettina B Handschin Christoph C

PloS one 20160727 7

The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic ...[more]

PMID: 27463191

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Project description:BackgroundThe relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of multiple days is considered to be an accurate method.MethodsWe included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis.ResultsAmong 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval [CI], 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94).ConclusionsHigher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).

Dataset Information

Loss of Renal Tubular PGC-1? Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

Publications

Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

Similar Datasets

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