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Decrease in irisin in patients with chronic kidney disease.

Wen MS, Wang CY, Lin SL, Hung KC - PLoS ONE (2013)

Bottom Line: The decrease in irisin levels was inversely correlated with the levels of blood urea nitrogen and creatinine.Further association analysis revealed that irisin level is independently associated with high-density lipoprotein cholesterol level.Our results suggest that chronic kidney disease patients have lower than normal irisin levels at rest.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taoyuan, Taiwan. ocean.laboratory@me.com

ABSTRACT
Patients with chronic kidney disease have abnormal energy expenditure and metabolism. The mechanisms underlying altered energy expenditure in uremia are unknown and remain to be elucidated. Irisin is a peroxisome proliferator-activated receptor γ coactivator 1-α-dependent myokine, and it increases energy expenditure in the absence of changes in food intake or activity. We hypothesize that chronic kidney disease patients have altered irisin levels. We measured resting irisin levels in 38 patients with stage 5 chronic kidney disease and in 19 age- and sex-matched normal subjects. Plasma irisin levels were significantly decreased in chronic kidney disease patients (58.59%; 95% CI 47.9%-69.2%, p<0.0001). The decrease in irisin levels was inversely correlated with the levels of blood urea nitrogen and creatinine. Further association analysis revealed that irisin level is independently associated with high-density lipoprotein cholesterol level. Our results suggest that chronic kidney disease patients have lower than normal irisin levels at rest. Furthermore, irisin may play a major role in affecting high-density lipoprotein cholesterol levels and abnormal energy expenditure in chronic kidney disease patients.

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Related in: MedlinePlus

Indoxyl sulfate modulates FNDC5 expression in skeletal muscle cells.A, Dose-response relationship for the decrease in FNDC5 expression in skeletal muscle cells treated with indoxyl sulfate for 24 h. (n = 3; *, p<0.05) B, PGC-1α expression analysis by western blot of skeletal muscle cells treated with indoxyl sulfate for 24 h.
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pone-0064025-g002: Indoxyl sulfate modulates FNDC5 expression in skeletal muscle cells.A, Dose-response relationship for the decrease in FNDC5 expression in skeletal muscle cells treated with indoxyl sulfate for 24 h. (n = 3; *, p<0.05) B, PGC-1α expression analysis by western blot of skeletal muscle cells treated with indoxyl sulfate for 24 h.

Mentions: We next tested whether uremic toxin has a direct effect on the expression of irisin in skeletal muscle cells. Indoxyl sulfate, which is a protein-bound uremic toxin, increases significantly during kidney function deterioration.[20] Recent studies showed that the levels of indoxyl sulfate are associated with kidney disease progression and mortality in CKD patients. [21], [22] We treated human skeletal muscle cells with indoxyl sulfate at different concentrations (0, 50, 250 and 500 µM) for 24 h. In these cells, FNDC5 protein levels decreased in a dose-dependent manner after 24 h treatment of indoxyl sulfate. (Fig. 2A) The PGC1-α protein levels were not altered by indoxyl sulfate. (Fig. 2B) The irisin released into the culture medium of human skeletal muscle cells or differentiated C2C12 myoblasts, measured by the irisin assay kit after 24 h treatment of 500 µM indoxyl sulfate, were also significantly decreased when compared with controls (36.3±2.3 ng/mL vs 57.8±2.1 ng/mL, p = 0.01).


Decrease in irisin in patients with chronic kidney disease.

Wen MS, Wang CY, Lin SL, Hung KC - PLoS ONE (2013)

Indoxyl sulfate modulates FNDC5 expression in skeletal muscle cells.A, Dose-response relationship for the decrease in FNDC5 expression in skeletal muscle cells treated with indoxyl sulfate for 24 h. (n = 3; *, p<0.05) B, PGC-1α expression analysis by western blot of skeletal muscle cells treated with indoxyl sulfate for 24 h.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646802&req=5

pone-0064025-g002: Indoxyl sulfate modulates FNDC5 expression in skeletal muscle cells.A, Dose-response relationship for the decrease in FNDC5 expression in skeletal muscle cells treated with indoxyl sulfate for 24 h. (n = 3; *, p<0.05) B, PGC-1α expression analysis by western blot of skeletal muscle cells treated with indoxyl sulfate for 24 h.
Mentions: We next tested whether uremic toxin has a direct effect on the expression of irisin in skeletal muscle cells. Indoxyl sulfate, which is a protein-bound uremic toxin, increases significantly during kidney function deterioration.[20] Recent studies showed that the levels of indoxyl sulfate are associated with kidney disease progression and mortality in CKD patients. [21], [22] We treated human skeletal muscle cells with indoxyl sulfate at different concentrations (0, 50, 250 and 500 µM) for 24 h. In these cells, FNDC5 protein levels decreased in a dose-dependent manner after 24 h treatment of indoxyl sulfate. (Fig. 2A) The PGC1-α protein levels were not altered by indoxyl sulfate. (Fig. 2B) The irisin released into the culture medium of human skeletal muscle cells or differentiated C2C12 myoblasts, measured by the irisin assay kit after 24 h treatment of 500 µM indoxyl sulfate, were also significantly decreased when compared with controls (36.3±2.3 ng/mL vs 57.8±2.1 ng/mL, p = 0.01).

Bottom Line: The decrease in irisin levels was inversely correlated with the levels of blood urea nitrogen and creatinine.Further association analysis revealed that irisin level is independently associated with high-density lipoprotein cholesterol level.Our results suggest that chronic kidney disease patients have lower than normal irisin levels at rest.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taoyuan, Taiwan. ocean.laboratory@me.com

ABSTRACT
Patients with chronic kidney disease have abnormal energy expenditure and metabolism. The mechanisms underlying altered energy expenditure in uremia are unknown and remain to be elucidated. Irisin is a peroxisome proliferator-activated receptor γ coactivator 1-α-dependent myokine, and it increases energy expenditure in the absence of changes in food intake or activity. We hypothesize that chronic kidney disease patients have altered irisin levels. We measured resting irisin levels in 38 patients with stage 5 chronic kidney disease and in 19 age- and sex-matched normal subjects. Plasma irisin levels were significantly decreased in chronic kidney disease patients (58.59%; 95% CI 47.9%-69.2%, p<0.0001). The decrease in irisin levels was inversely correlated with the levels of blood urea nitrogen and creatinine. Further association analysis revealed that irisin level is independently associated with high-density lipoprotein cholesterol level. Our results suggest that chronic kidney disease patients have lower than normal irisin levels at rest. Furthermore, irisin may play a major role in affecting high-density lipoprotein cholesterol levels and abnormal energy expenditure in chronic kidney disease patients.

Show MeSH
Related in: MedlinePlus