Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production

Nature Communications

Volumn 2, Issue 1, 2011, Pages

  Teng, Ruifeng ^a   Gavrilova, Oksana ^a   Suzuki, Norio ^b   Chanturiya, Tatyana ^a   Schimel, Daniel ^c   Hugendubler, Lynne ^a   Mammen, Selin ^a   Yver, Dena R ^a   Cushman, Samuel W ^a   Mueller, Elisabetta ^a   Yamamoto, Masayuki ^b   Hsu, Lewis L ^d   Noguchi, Constance Tom ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^d CHILDREN'S NATIONAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPONECTIN; ERYTHROPOIETIN RECEPTOR; LEPTIN; PEPTIDE HORMONE; PROOPIOMELANOCORTIN; ERYTHROPOIETIN;

ADIPOCYTE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY WEIGHT; BRAIN NERVE CELL; CELL DIFFERENTIATION; CONTROLLED STUDY; ENERGY EXPENDITURE; FEMALE; FOOD INTAKE; HEMATOPOIETIC TISSUE; HOMEOSTASIS; HYPOTHALAMUS; INSULIN RESISTANCE; LIPID STORAGE; MALE; MOUSE; NONHUMAN; OBESITY; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; WHITE ADIPOSE TISSUE; ANIMAL; C57BL MOUSE; DRUG EFFECT; GENETICS; IMMUNOHISTOCHEMISTRY; METABOLISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENIC MOUSE; WESTERN BLOTTING;

MUS;

ANIMALS; BLOTTING, WESTERN; ERYTHROPOIETIN; FEMALE; HYPOTHALAMUS; IMMUNOHISTOCHEMISTRY; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; OBESITY; PRO-OPIOMELANOCORTIN; RECEPTORS, ERYTHROPOIETIN; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 84855703353     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms1526     Document Type: Article

References (50)

1. Ellacott, K. L., Morton, G. J., Woods, S. C., Tso, P. & Schwartz, M. W. Assessment of feeding behavior in laboratory mice. Cell Metab. 12, 10-17 (2010).
2. Hamilton, M. T., Hamilton, D. G. & Zderic, T. W. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes 56, 2655-2667 (2007). (Pubitemid 350063956)
3. Kapitsinou, P. P. et al. Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia. Blood 116, 3039-3048.
4. Syed, R. S. et al. Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature 395, 511-516 (1998). (Pubitemid 28462447)
5. Nagata, Y., Takahashi, N., Davis, R. J. & Todokoro, K. Activation of p38 MAP kinase and JNK but not ERK is required for erythropoietin-induced erythroid differentiation. Blood 92, 1859-1869 (1998). (Pubitemid 28446674)
6. Zhang, J. & Lodish, H. F. Constitutive activation of the MEK/ERK pathway mediates all effects of oncogenic H-ras expression in primary erythroid progenitors. Blood 104, 1679-1687 (2004). (Pubitemid 39202274)
7. Zhang, Y. L. et al. Symmetric signaling by an asymmetric 1 erythropoietin: 2 erythropoietin receptor complex. Mol. Cell 33, 266-274 (2009).
8. Wu, H., Liu, X., Jaenisch, R. & Lodish, H. F. Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 83, 59-67 (1995).
9. Yu, X. et al. Erythropoietin receptor signalling is required for normal brain development. Development 129, 505-516 (2002). (Pubitemid 34863815)
10. Wu, H., Lee, S. H., Gao, J., Liu, X. & Iruela-Arispe, M. L. Inactivation of erythropoietin leads to defects in cardiac morphogenesis. Development 126, 3597-3605 (1999). (Pubitemid 29419516)
11. Kertesz, N., Wu, J., Chen, T. H., Sucov, H. M. & Wu, H. The role of erythropoietin in regulating angiogenesis. Dev. Biol. 276, 101-110 (2004). (Pubitemid 39452849)
12. Suzuki, N. et al. Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality. Blood 100, 2279-2288 (2002).
13. Morita, M. et al. HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J. 22, 1134-1146 (2003). (Pubitemid 36313597)
14. Satoh, K. et al. Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice. Circulation 113, 1442-1450 (2006). (Pubitemid 43739441)
15. Lin, C. S., Lim, S. K., D'Agati, V. & Costantini, F. Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis. Genes Dev. 10, 154-164 (1996).
16. Hojman, P. et al. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles. PLoS One 4, e5894 (2009).
17. Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S. & Goldstein, J. L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401, 73-76 (1999).
18. Kubota, N. et al. Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab. 6, 55-68 (2007). (Pubitemid 47007437)
19. Hu, E., Kim, J. B., Sarraf, P. & Spiegelman, B. M. Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma. Science 274, 2100-2103 (1996). (Pubitemid 27020707)
20. Nanbu-Wakao, R. et al. Stimulation of 3T3-L1 adipogenesis by signal transducer and activator of transcription 5. Mol. Endocrinol. 16, 1565-1576 (2002). (Pubitemid 34743675)
21. Schwartz, M. W., Woods, S. C., Porte, D. Jr, Seeley, R. J. & Baskin, D. G. Central nervous system control of food intake. Nature 404, 661-671 (2000). (Pubitemid 30205071)
22. Wess, J., Eglen, R. M. & Gautam, D. Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat. Rev. Drug Discov. 6, 721-733 (2007). (Pubitemid 47342315)
23. Yasuda, Y. et al. Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis. J. Biol. Chem. 273, 25381-25387 (1998). (Pubitemid 28443305)
24. Simler, N., Grosfeld, A., Peinnequin, A., Guerre-Millo, M. & Bigard, A. X. Leptin receptor-deficient obese Zucker rats reduce their food intake in response to hypobaric hypoxia. Am. J. Physiol. Endocrinol. Metab. 290, E591-597 (2006). (Pubitemid 43671708)
25. Bailey, D. M., Ainslie, P. N., Jackson, S. K., Richardson, R. S. & Ghatei, M. Evidence against redox regulation of energy homoeostasis in humans at high altitude. Clin. Sci. (Lond.) 107, 589-600 (2004). (Pubitemid 39627206)
26. Belgardt, B. F. et al. PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response. Cell Metab. 7, 291-301 (2008). (Pubitemid 351467391)
27. Yamada, M. et al. Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature 410, 207-212 (2001). (Pubitemid 32216592)
28. Mesaros, A. et al. Activation of Stat3 signaling in AgRP neurons promotes locomotor activity. Cell Metab. 7, 236-248 (2008). (Pubitemid 351297558)
29. Challis, B. G. et al. Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36). Proc. Natl Acad. Sci. USA 101, 4695-4700 (2004). (Pubitemid 38437473)
30. Lu, M. et al. Brain PPAR-gamma promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones. Nat. Med. 17, 618-622 (2011).
31. Ryan, K. K. et al. A role for central nervous system PPAR-gamma in the regulation of energy balance. Nat. Med. 17, 623-626 (2011).
32. Sui, X., Krantz, S. B., You, M. & Zhao, Z. Synergistic activation of MAP kinase (ERK1/2) by erythropoietin and stem cell factor is essential for expanded erythropoiesis. Blood 92, 1142-1149 (1998). (Pubitemid 28369026)
33. Camp, H. S. & Tafuri, S. R. Regulation of peroxisome proliferator-activated receptor gamma activity by mitogen-activated protein kinase. J. Biol. Chem. 272, 10811-10816 (1997). (Pubitemid 27181096)
34. Spalding, K. L. et al. Dynamics of fat cell turnover in humans. Nature 453, 783-787 (2008). (Pubitemid 351793777)
35. Carnevalli, L. S. et al. S6K1 plays a critical role in early adipocyte differentiation. Dev. Cell 18, 763-774 (2010).
36. Zhang, J. W., Tang, Q. Q., Vinson, C. & Lane, M. D. Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes. Proc. Natl Acad. Sci. USA 101, 43-47 (2004). (Pubitemid 38084200)
37. Rangwala, S. M. et al. Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivity. Dev. Cell 5, 657-663 (2003). (Pubitemid 37243053)
38. Yamauchi, T. et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat. Med. 13, 332-339 (2007). (Pubitemid 46376688)
39. Yamauchi, T. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941-946 (2001). (Pubitemid 32756432)
40. Nairz, M. et al. Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-kappaB-inducible immune pathways. Immunity 34, 61-74 (2011).
41. Jubinsky, P. T., Krijanovski, O. I., Nathan, D. G., Tavernier, J. & Sieff, C. A. The beta chain of the interleukin-3 receptor functionally associates with the erythropoietin receptor. Blood 90, 1867-1873 (1997). (Pubitemid 27377296)
42. Brines, M. et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc. Natl Acad. Sci. USA 101, 14907-14912 (2004). (Pubitemid 39410773)
43. Sautina, L. et al. Induction of nitric oxide by erythropoietin is mediated by the β common receptor and requires interaction with VEGF receptor 2. Blood 115, 896-905 (2009).
44. Yu, S. et al. Paternal versus maternal transmission of a stimulatory G-protein alpha subunit knockout produces opposite effects on energy metabolism. J. Clin. Invest. 105, 615-623 (2000). (Pubitemid 30146508)
45. McLaughlin, T. et al. Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia 50, 1707-1715 (2007). (Pubitemid 47036653)
46. Elliott, S. et al. Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood 107, 1892-1895 (2006). (Pubitemid 43289368)
47. Kirkeby, A., van Beek, J., Nielsen, J., Leist, M. & Helboe, L. Functional and immunochemical characterisation of different antibodies against the erythropoietin receptor. J. Neurosci. Methods 164, 50-58 (2007). (Pubitemid 46935964)
48. D'Andrea, A. D., Rup, B. J., Fisher, M. J. & Jones, S. Anti-erythropoietin receptor (EPO-R) monoclonal antibodies inhibit erythropoietin binding and neutralize bioactivity. Blood 82, 46-52 (1993). (Pubitemid 23188745)
49. Anagnostou, A. et al. Erythropoietin receptor mRNA expression in human endothelial cells. Proc. Natl Acad. Sci. USA 91, 3974-3978 (1994). (Pubitemid 24139555)
50. Brewer, G. J. & Torricelli, J. R. Isolation and culture of adult neurons and neurospheres. Nat. Protoc. 2, 1490-1498 (2007). (Pubitemid 46952327)