Abstract
BackgroundErythropoietin (Epo) exerts direct effects on white adipose tissue (WAT) in mice in addition to its erythropoietic effects, and in humans Epo increases resting energy expenditure and affect serum lipid levels, but direct effects of Epo in human WAT have not been documented. We therefore investigated the effects of acute and prolonged Epo exposure on human WAT in vivo.MethodData were obtained from two clinical trials: 1) acute Epo exposure (rHuEpo, 400 IU/kg) followed by WAT biopsies after 1 h and 2) 10 weeks treatment with the erythropoiesis-stimulating agent (ESA) Darbepoietin-alpha. Biopsies were analyzed by PCR for Epo receptor (Epo-R) mRNA. A new and highly specific antibody (A82, Amgen) was used to evaluate the presence of Epo-R by western blot analysis in addition to Epo-R signaling proteins (Akt, STAT5, p70s6k, LYN, and p38MAPK), activation of lipolytic pathways (ATGL, HSL, CGI-58, G0S2, Perilipin, Cidea, Cidec, AMPK, and ACC), and mitochondrial biogenesis (VDAC, HSP90, PDH, and SDHA).ResultsNo evidence of in vivo activation of the Epo-R in WAT could be documented despite detectable levels of Epo-R mRNA.ConclusionThus, in contradiction to animal studies, Epo treatment within a physiological relevant range in humans does not exert direct effects in a subcutaneous WAT.
Highlights
Erythropoietin (Epo) exerts direct effects on white adipose tissue (WAT) in mice in addition to its erythropoietic effects, and in humans Epo increases resting energy expenditure and affect serum lipid levels, but direct effects of Epo in human WAT have not been documented
No evidence of in vivo activation of the Epo receptors (Epo-R) in WAT could be documented despite detectable levels of Epo-R mRNA
Epo-R mRNA and protein in subcutaneous WAT Epo-R mRNA was detected in WAT from all subjects, as well as in the positive K-562 cells
Summary
Erythropoietin (Epo) exerts direct effects on white adipose tissue (WAT) in mice in addition to its erythropoietic effects, and in humans Epo increases resting energy expenditure and affect serum lipid levels, but direct effects of Epo in human WAT have not been documented. We investigated the effects of acute and prolonged Epo exposure on human WAT in vivo. Prolonged treatment to healthy humans with an erythropoiesis-stimulating agent (ESA) significantly increases serum FFA levels and hepatic lipid content [7]. Mice with a lack of Epo-R, except for the bone marrow, have a significantly higher body weight, increased fat mass and increased serum TG levels [2, 9]. A reduction in body weight due to reduced WAT mass in obese mice is found after Epo treatment [2, 8,9,10,11]
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