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      No effect of 10 weeks erythropoietin treatment on lipid oxidation in healthy men

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          Abstract

          Studies indicate that erythropoietin (EPO) has effect on lipid and energy metabolism; however, the impact of EPO on lipid oxidation in vivo has not been well documented. Here, we evaluate whether long-term erythropoiesis-stimulating agent (ESA) treatment affects the oxidation of plasma very low-density lipoprotein triglycerides (VLDL-TG) fatty acids (FA), plasma free fatty acids (FFA) and non-plasma (residual) FA in healthy, young, sedentary men. Infusion of [1- 14C]VLDL-TG and [9,10- 3H]palmitate was used in combination with indirect calorimetry to assess resting lipid fuel utilization and kinetics, and resting energy expenditure (REE) before and after 10 weeks of ESA exposure compared with placebo. REE increased significantly during ESA compared with placebo ( P = 0.023, RM-ANOVA). Oxidation rates of VLDL-TG FA, FFA, and residual FA remained unchanged during ESA compared with placebo. The relative contribution of the lipid stores was greatest for FFA (47.1%) and the total lipid oxidation rate and was not significantly different between ESA and placebo-treated subjects. We conclude that long-term ESA treatment of healthy young men increases REE but does not alter the oxidation rates of plasma and non-plasma FA sources.

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          Most cited references38

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          Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial.

          We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis. The recombinant human erythropoietin was given intravenously three times weekly after dialysis, and transfusion requirements, hematocrit, ferrokinetics, and reticulocyte responses were monitored. Over a range of doses between 15 and 500 units per kilogram of body weight, dose-dependent increases in effective erythropoiesis were noted. At 500 units per kilogram, changes in the hematocrit of as much as 10 percentage points were seen within three weeks, and increases in ferrokinetics of three to four times basal values, as measured by erythron transferrin uptake, were observed. Of 18 patients receiving effective doses of recombinant human erythropoietin, 12 who had required transfusions no longer needed them, and in 11 the hematocrit increased to 35 percent or more. Along with the rise in hematocrit, four patients had an increase in blood pressure, and a majority had increases in serum creatinine and potassium levels. No organ dysfunction or other toxic effects were observed, and no antibodies to the recombinant hormone were formed. These results demonstrate that recombinant human erythropoietin is effective, can eliminate the need for transfusions with their risks of immunologic sensitization, infection, and iron overload, and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease.
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            Erythropoietin treatment leads to reduced blood glucose levels and body mass: insights from murine models.

            Erythropoietin (EPO) regulates proliferation and differentiation of erythroid precursor cells into erythrocytes. The last decade has revealed non-renal sites of EPO production and extrahematopoietic expression of the EPO receptor, thus suggesting that EPO has pleiotropic functions. Here, we addressed the interplay between EPO/glucose metabolism/body weight by employing a panel of relevant experimental murine models. The models focused on situations of increased EPO levels, including EPO-injected C57BL/6 and BALB/c mice, as well as transgenic mice (tg6) constitutively overexpressing human EPO, thus exposed to constantly high EPO serum levels. As experimental models for diabetes and obesity, we employed protein Tyr phosphatase 1B (PTP1B) knockout mice associated with resistance to diabetes (PTP1B(-/-)), and ob/ob mice susceptible to diabetes and obesity. The data presented herein demonstrate EPO-mediated decrease in blood glucose levels in all mice models tested. Moreover, in the ob/ob mice, we observed EPO-mediated attenuation of body weight gain and reduction of hemoglobin A1c. Taken together, our data bear significant clinical implications of EPO treatment in the management of a wide range of metabolic diseases, thus adding an important novel therapeutic potential to this pleiotropic hormone.
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              Effect of sex and obesity on basal VLDL-triacylglycerol kinetics.

              Plasma fatty acid availability is a major regulator of VLDL-triacylglycerol production. Basal whole-body lipolysis is higher in women than in men and is higher in persons with abdominal obesity than in lean individuals. Our goal was to determine whether sex and abdominal obesity affect VLDL-triacylglycerol kinetics. We hypothesized that basal VLDL-triacylglycerol production would be greater in women than in men and greater in obese than in lean subjects. VLDL-triacylglycerol kinetics were measured in 20 lean (10 men, 10 women; body mass index, in kg/m(2): 23 +/- 1) and 20 abdominally obese (10 men, 10 women; body mass index: 35 +/- 1) subjects by using a bolus injection of [(2)H(5)]glycerol and compartmental modeling analysis. The rate of VLDL-triacylglycerol secretion was greater in the lean women than in the lean men (5.1 +/- 0.7 and 2.6 +/- 0.3 micro mol x L plasma(-1) x min(-1), respectively; P < 0.002). Obesity was associated with increased VLDL-triacylglycerol secretion in the men (P < 0.001) but not in the women, which resulted in greater rates of VLDL-triacylglycerol secretion in the obese men than in the obese women (6.8 +/- 0.5 and 5.0 +/- 0.5 micro mol x L plasma(-1) x min(-1), respectively; P < 0.05). The clearance of VLDL-triacylglycerol from plasma was greater (P < 0.05) in the lean women than in the lean men (42 +/- 7 and 27 +/- 4 mL plasma/min, respectively) or in the obese men and obese women (28 +/- 3 and 20 +/- 4 mL plasma/min, respectively). The plasma VLDL-triacylglycerol concentration was directly related to the rate of VLDL-triacylglycerol secretion in the men (R(2) = 0.79, P < 0.001) and inversely related to VLDL-triacylglycerol clearance in the women (R(2) = 0.84, P<0.001). Sex and obesity have independent effects on basal VLDL-triacylglycerol kinetics.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                December 2020
                13 October 2020
                : 9
                : 12
                : 1148-1155
                Affiliations
                [1 ]Department of Endocrinology and Internal Medicine , Aarhus University Hospital, Aarhus, Denmark
                [2 ]Department of Rheumatology , Diakonhjemmet Hospital, Oslo, Norway
                [3 ]Steno Diabetes Center Aarhus , Aarhus University Hospital, Aarhus, Denmark
                Author notes
                Correspondence should be addressed to S Nielsen: nielsen.soren@ 123456dadlnet.dk
                Author information
                http://orcid.org/0000-0002-4195-6231
                Article
                EC-20-0305
                10.1530/EC-20-0305
                7774772
                33112835
                34202e32-9b2f-4a99-b453-37a80ea9c693
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 18 August 2020
                : 13 October 2020
                Categories
                Research

                erythropoietin,lipids,vldl-tg,energy expenditure
                erythropoietin, lipids, vldl-tg, energy expenditure

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