Christensen Britt, Nellemann Birgitte, Jørgensen Jens Otto L, Pedersen Steen B, Jessen Niels
Department of Endocrinology and Internal Medicine, NBG/THG, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
Lipids Health Dis. 2016 Sep 17;15(1):160. doi: 10.1186/s12944-016-0327-z.
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 therefore investigated the effects of acute and prolonged Epo exposure on human WAT in vivo.
Data 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).
No evidence of in vivo activation of the Epo-R in WAT could be documented despite detectable levels of Epo-R mRNA.
Thus, in contradiction to animal studies, Epo treatment within a physiological relevant range in humans does not exert direct effects in a subcutaneous WAT.
促红细胞生成素（Epo）除了具有促红细胞生成作用外，还对小鼠白色脂肪组织（WAT）产生直接影响，并且在人类中，Epo可增加静息能量消耗并影响血清脂质水平，但Epo对人类WAT的直接影响尚未得到证实。因此，我们研究了急性和长期Epo暴露对人体WAT的体内影响。
数据来自两项临床试验：1）急性Epo暴露（重组人促红细胞生成素，400 IU/kg），1小时后进行WAT活检；2）使用促红细胞生成刺激剂（ESA）达贝泊汀-α进行10周治疗。通过PCR分析活检组织中促红细胞生成素受体（Epo-R）mRNA。除了Epo-R信号蛋白（Akt、STAT5、p70s6k、LYN和p38MAPK）、脂解途径激活（ATGL、HSL、CGI-58、G0S2、 perilipin、Cidea、Cidec、AMPK和ACC）以及线粒体生物发生（VDAC、HSP90、PDH和SDHA）外，还使用一种新的高特异性抗体（A82，安进公司）通过蛋白质印迹分析评估Epo-R的存在。
尽管可检测到Epo-R mRNA水平，但未发现WAT中Epo-R在体内激活的证据。
因此，与动物研究相反，在生理相关范围内对人类进行Epo治疗不会对皮下WAT产生直接影响。
