The Effect of Treatment with Recombinant Human Erythropoietin on the Histological Appearance and Glycogen Content of Skeletal Muscle in Patients with Chronic Renal Failure Treated by Regular Hospital Haemodialysis

Davenport, Andrew; King, Rhodri; Ironside, Jennifer; Will, Eric J.; Davison, A. M.

doi:10.1159/000187284

Cited by 27 publications

(22 citation statements)

References 19 publications

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“…In support of this Davenport et al showed that 14 weeks of EPO administration in haemodialysis patients increased muscle glycogen content and lowered muscle fat content [21], while Cayla et al showed that EPO induces a shift in muscle fibre composition from fast glycolytic fibres to slow oxidative fibres [22]. This suggests that EPO is indeed involved in shifting muscle metabolism towards increasing fat oxidation.…”

Section: Discussionmentioning

confidence: 94%

Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles

et al. 2009

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Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9±0.8 g (control, normal diet,) 21.9±1.4 g (EPO, normal diet), 35.3±3.3 g (control, high-fat diet) and 28.8±2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

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Section: Discussionmentioning

confidence: 94%

Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles

et al. 2009

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“…Grossly altered muscle fiber size and fiber type distribution are seen in both patients with CKD (34,35) and hemodialysis patients (36,37). It is interesting that these can be improved not only with exercise training (38,39) but also when [Hb] is increased with erythropoietin treatment (40). In addition to fiber changes, the amount of contractile tissue will have an impact on exercise performance.…”

Section: Discussionmentioning

confidence: 99%

Exercise Performance Falls over Time in Patients with Chronic Kidney Disease Despite Maintenance of Hemoglobin Concentration

Leikis

McKenna

Petersen

et al. 2006

Clinical Journal of the American Society of Nephrology

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Physical function is limited in patients with kidney disease, although previous studies have been confounded by anemia. What is not clear is how physical performance changes over time as renal function deteriorates. A cohort of 12 patients (10 male, two female; mean ؎ SD age 49 ؎ 11 yr) who had stages 3 to 4 chronic kidney disease without previous anemia were examined, and nine were followed for a 2-yr period. Assessments were made of peak oxygen consumption (VO 2peak ) by cycle ergometry, leg extension strength, and fatigue on an isokinetic dynamometer and thigh muscle cross-sectional area (TMCSA) by computed tomography. At baseline, creatinine clearance was 31 ؎ 13 ml/min and hemoglobin concentration ([Hb]) was 129 ؎ 9g/L. VO 2peak was low (1.88 L/min, 82% of predicted), and maximal isometric voluntary contraction was 188 ؎ 42 Nm, with a TMCSA of 144 ؎ 27 cm 2 . VO 2peak correlated with creatinine clearance corrected for body surface area (r ‫؍‬ 0.613, P ‫؍‬ 0.034) but not to [Hb]. VO 2peak adjusted for patient weight correlated with leg fatigue (r ‫؍‬ ؊0.693, P ‫؍‬ 0.012). For those with follow-up tests, there were falls in renal function by 28% (P ‫؍‬ 0.007) and VO 2peak by 9% (P ‫؍‬ 0.03), whereas [Hb] did not change. Leg strength fell across a range of isokinetic speeds (P ‫؍‬ 0.04), whereas no change in TMCSA was observed. In conclusion, exercise performance as measured by aerobic (VO 2peak ) and leg strength tests were reduced in patients with stages 3 to 4 chronic kidney disease. As renal function declined over time, there was a corresponding decline in exercise performance even when [Hb] was maintained.

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“…Fourteen weeks of EPO treatment had no effect on either muscle fiber hypertrophy or angiogenesis (Lundby et al, 2008b). Interestingly, it has been reported that patients with chronic renal failure treated with EPO showed an increase in muscle fiber diameter, especially in type I fibers, as well as an increase in glycogen content when compared to non-treated patients (Davenport et al, 1993). Long term EPO treatment had no effect on the muscle membrane transport system, on the enzymes involved in pH regulation or on the majority of proteins involved in acid–base balance.…”

Section: Effects Of Epo In Skeletal Musclementioning

confidence: 99%

The role and regulation of erythropoietin (EPO) and its receptor in skeletal muscle: how much do we really know?

Lamon¹,

Russell²

2013

Front. Physiol.

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Erythropoietin (EPO) primarily activates erythroid cell proliferation and growth and is active in several types of non-hematopoietic cells via its interaction with the EPO-receptor (EPO-R). This review focuses on the role of EPO in skeletal muscle. The EPO-R is expressed in skeletal muscle cells and EPO may promote myoblast differentiation and survival via the activation of the same signaling cascades as in hematopoietic cells, such as STAT5, MAPK and Akt. Inconsistent results exist with respect to the detection of the EPO-R mRNA and protein in muscle cells, tissue and across species and the use of non-specific EPO-R antibodies contributes to this problem. Additionally, the inability to reproducibly detect an activation of the known EPO-induced signaling pathways in skeletal muscle questions the functionality of the EPO-R in muscle in vivo. These equivocal findings make it difficult to distinguish between a direct effect of EPO on skeletal muscle, via the activation of its receptor, and an indirect effect resulting from a better oxygen supply to the muscle. Consequently, the precise role of EPO in skeletal muscle and its regulatory mechanism/s remain to be elucidated. Further studies are required to comprehensively establish the importance of EPO and its function in skeletal muscle health.

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The Effect of Treatment with Recombinant Human Erythropoietin on the Histological Appearance and Glycogen Content of Skeletal Muscle in Patients with Chronic Renal Failure Treated by Regular Hospital Haemodialysis

Cited by 27 publications

References 19 publications

Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles

Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles

Exercise Performance Falls over Time in Patients with Chronic Kidney Disease Despite Maintenance of Hemoglobin Concentration

The role and regulation of erythropoietin (EPO) and its receptor in skeletal muscle: how much do we really know?

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