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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.
AuthorsRuifeng Teng, Oksana Gavrilova, Norio Suzuki, Tatyana Chanturiya, Daniel Schimel, Lynne Hugendubler, Selin Mammen, Dena R Yver, Samuel W Cushman, Elisabetta Mueller, Masayuki Yamamoto, Lewis L Hsu, Constance Tom Noguchi
JournalNature communications (Nat Commun) Vol. 2 Pg. 520 (Nov 01 2011) ISSN: 2041-1723 [Electronic] England
PMID22044999 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Receptors, Erythropoietin
  • Erythropoietin
  • Pro-Opiomelanocortin
Topics
  • Animals
  • Blotting, Western
  • Erythropoietin (pharmacology)
  • Female
  • Hypothalamus (drug effects, metabolism)
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Obesity (etiology, metabolism)
  • Pro-Opiomelanocortin (metabolism)
  • Receptors, Erythropoietin (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction

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