Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production

Ruifeng 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

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

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.

Original languageEnglish
Article number520
JournalNature communications
Volume2
Issue number1
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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