Erythropoietin has shown beneficial effects in the regulation of obesity and metabolic syndrome. We created the mice with adipocyte specific deletion of erythropoietin receptor. These mice exhibited obesity and decreased glucose tolerance and insulin sensitivity especially on high fat diet. Erythropoietin treatment in wild type mice subjected to diet induced obesity increased oxidative metabolism, fatty acid oxidation and key metabolic genes in adipocytes as well as in white adipose tissue from diet induced obese wild type mice. Erythropoietin induced increase in metabolic activity is associated with induction of brown fat like features in white adipocytes as demonstrated by increases in brown fat gene expression, mitochondrial content and uncoupled respiration. PPARalpha was found to mediate erythropoietin activity. PPARalpha cooperates with Sirt1 activated by erythropoietin through modulating NAD+ level to regulate metabolic activity and Sirt1 knock down also attenuated adipose response to erythropoietin. These findings suggest erythropoietin signaling may provide a potential therapeutic strategy to protect against obesity and metabolic disorders.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$782,950
Indirect Cost
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State
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Alnaeeli, Mawadda; Noguchi, Constance Tom (2015) Erythropoietin and obesity-induced white adipose tissue inflammation: redefining the boundaries of the immunometabolism territory. Adipocyte 4:153-7
Wang, Li; Di, Lijun; Noguchi, Constance Tom (2014) Erythropoietin, a novel versatile player regulating energy metabolism beyond the erythroid system. Int J Biol Sci 10:921-39
Wang, Li; Di, Lijun; Noguchi, Constance Tom (2014) AMPK is involved in mediation of erythropoietin influence on metabolic activity and reactive oxygen species production in white adipocytes. Int J Biochem Cell Biol 54:1-9
Alnaeeli, Mawadda; Raaka, Bruce M; Gavrilova, Oksana et al. (2014) Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity. Diabetes 63:2415-31
Zhang, Yuanyuan; Wang, Li; Dey, Soumyadeep et al. (2014) Erythropoietin action in stress response, tissue maintenance and metabolism. Int J Mol Sci 15:10296-333
Wang, Li; Teng, Ruifeng; Di, Lijun et al. (2013) PPARα and Sirt1 mediate erythropoietin action in increasing metabolic activity and browning of white adipocytes to protect against obesity and metabolic disorders. Diabetes 62:4122-31
Foskett, Amanda; Alnaeeli, Mawadda; Wang, Li et al. (2011) The effects of erythropoietin dose titration during high-fat diet-induced obesity. J Biomed Biotechnol 2011:373781