title: Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production.
abstract: Although erythropoietin (Epo) is the cytokine known to regulate erythropoiesis, erythropoietin receptor (EpoR) expression and associated activity beyond haematopoietic tissue remain uncertain. Here we show that mice with EpoR expression restricted to haematopoietic tissues (Tg) develop obesity and insulin resistance. Tg-mice exhibit a decrease in energy expenditure and an increase in white fat mass and adipocyte number. Conversely, Epo treatment of wild-type (WT)-mice increases energy expenditure and reduces food intake and fat mass accumulation but shows no effect in body weight of Tg-mice. EpoR is expressed at a high level in white adipose tissue and in the proopiomelanocortin (POMC) neurons of the hypothalamus. Although Epo treatment in WT-mice induces the expression of the polypeptide hormone precursor, POMC, mice lacking EpoR show reduced levels of POMC in the hypothalamus. This study provides the first evidence that mice lacking EpoR in non-haematopoietic tissue become obese and insulin resistant with loss of Epo regulation of energy homeostasis.
authors: Molecular Cell Biology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
authors: Ruifeng
authors: R
authors: Teng
authors: Oksana
authors: O
authors: Gavrilova
authors: Norio
authors: N
authors: Suzuki
authors: Tatyana
authors: T
authors: Chanturiya
authors: Daniel
authors: D
authors: Schimel
authors: Lynne
authors: L
authors: Hugendubler
authors: Selin
authors: S
authors: Mammen
authors: Dena R
authors: DR
authors: Yver
authors: Samuel W
authors: SW
authors: Cushman
authors: Elisabetta
authors: E
authors: Mueller
authors: Masayuki
authors: M
authors: Yamamoto
authors: Lewis L
authors: LL
authors: Hsu
authors: Constance Tom
authors: CT
authors: Noguchi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D011333:Pro-Opiomelanocortin