title: Nonerythropoietic Erythropoietin-Derived Peptide Suppresses Adipogenesis, Inflammation, Obesity and Insulin Resistance.
abstract: Erythropoietin (EPO) has been identified as being crucial for obesity modulation; however, its erythropoietic activity may limit its clinical application. EPO-derived Helix B-surface peptide (pHBSP) is nonerythrogenic but has been reported to retain other functions of EPO. The current study aimed to evaluate the effects and potential mechanisms of pHBSP in obesity modulation. We found that pHBSP suppressed adipogenesis, adipokine expression and peroxisome proliferator-activated receptor γ (PPARγ) levels during 3T3-L1 preadipocyte maturation through the EPO receptor (EPOR). In addition, also through EPOR, pHBSP attenuated macrophage inflammatory activation and promoted PPARγ expression. Furthermore, PPARγ deficiency partly ablated the anti-inflammatory activity of pHBSP in macrophages. Correspondingly, pHBSP administration to high-fat diet (HFD)-fed mice significantly improved obesity, insulin resistance (IR) and adipose tissue inflammation without stimulating hematopoiesis. Therefore, pHBSP can significantly protect against obesity and IR partly by inhibiting adipogenesis and inflammation. These findings have therapeutic implications for metabolic disorders, such as obesity and diabetes.
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Bangwei
authors.initials: B
authors.lastname: Luo
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Rongchen
authors.initials: R
authors.lastname: Shi
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People's Republic of China.
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004921:Erythropoietin / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*
chemical_list: D054392:Adipokines; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D047495:PPAR gamma; D010455:Peptides; D004921:Erythropoietin