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.

Background: Following treatment for breast cancer 12%–60% develop breast cancer-related lymphedema (BCRL). There are several ways of assessing BCRL. Circumference measurement (CM) and water displacement (WD) for volume measurements (VM) are frequently used methods in practice and research, respectively. The aim of this study was to evaluate CM and WD for VM of the BCRL arm and the contralateral arm, comparing the results with regional dual energy X-ray absorptiometry (DXA). Methods and Results: Twenty-four women with unilateral BCRL were included in the study. Blinded duplicate VM were obtained from both arms using the three methods mentioned above. CM and DXA were performed by two observers. WD was performed by a group of observers. Mean differences (d) in duplicated volumes, limits of agreement (LOA), and 95% confidence intervals (CI) were calculated for each method. The repeatability expressed as d (95% CI) between the duplicated VM of the BCRL arm and the contralateral arm was for DXA 3 ml (-6–11) and 3 ml (1–7), respectively. For CM and WD, the d (95% CI) of the BCRL arm were 107 ml (86–127) and 26 ml (-26–79), respectively and in the contralateral arm 100 ml (78–122) and −6 ml (-29–17), respectively. Conclusions: DXA is superior in repeatability when compared to CM and WD for VM, especially for the BCRL arm but also the contralateral arm.