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Here, we investigated the effects of a novel, selective ligand of this heterocomplex \u2013 pyroglutamate helix <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> surface peptide (<jats:styled-content style=\"fixed-case\">pHBSP<\/jats:styled-content>) \u2013 in mice fed a diet enriched in sugars and saturated fats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male <jats:styled-content style=\"fixed-case\">C57BL\/6J<\/jats:styled-content> mice were fed a high\u2010fat high\u2010sucrose diet (<jats:styled-content style=\"fixed-case\">HFHS<\/jats:styled-content>) for 22 weeks. <jats:styled-content style=\"fixed-case\">pHBSP<\/jats:styled-content> (30\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup> s.c.) was administered for the last 11 weeks. Biochemical assays, histopathological and immunohistochemical examinations and Western blotting were performed on serum and target organs (liver, kidney and skeletal muscle).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Mice fed with <jats:styled-content style=\"fixed-case\">HFHS<\/jats:styled-content> diet exhibited insulin resistance, hyperlipidaemia, hepatic lipid accumulation and kidney dysfunction. In gastrocnemius muscle, <jats:styled-content style=\"fixed-case\">HFHS<\/jats:styled-content> impaired the insulin signalling pathway and reduced membrane translocation of glucose transporter type 4 and glycogen content. Treatment with <jats:styled-content style=\"fixed-case\">pHBSP<\/jats:styled-content> ameliorated renal function, reduced hepatic lipid deposition, and normalized serum glucose and lipid profiles. These effects were associated with an improvement in insulin sensitivity and glucose uptake in skeletal muscle. Diet\u2010induced overproduction of the myokines <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and fibroblast growth factor\u201021 were attenuated by <jats:styled-content style=\"fixed-case\">pHBSP<\/jats:styled-content> and, most importantly, <jats:styled-content style=\"fixed-case\">pHBSP<\/jats:styled-content> markedly enhanced mitochondrial biogenesis in skeletal muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Chronic treatment of mice with an <jats:styled-content style=\"fixed-case\">EPO<\/jats:styled-content> derivative, devoid of haematopoietic effects, improved metabolic abnormalities induced by a high\u2010fat high\u2010sucrose diet, by affecting several levels of the insulin signalling and inflammatory cascades within skeletal muscle, while enhancing mitochondrial biogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12888","type":"journal-article","created":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T06:54:21Z","timestamp":1409208861000},"page":"5802-5815","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["RETRACTED: A non\u2010erythropoietic peptide derivative of erythropoietin decreases susceptibility to diet\u2010induced insulin resistance in mice"],"prefix":"10.1111","volume":"171","author":[{"given":"M","family":"Collino","sequence":"first","affiliation":[{"name":"Department of Drug Science and Technology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Benetti","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology University of Turin  Turin 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