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The therapeutic effect of chronic GIPR agonism to treat dyslipidemia and thus to reduce the cardiovascular disease risk independently of body weight loss has not been explored yet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After 8 weeks on western diet, LDL receptor knockout (LDLR-\/-) male mice were treated with daily subcutaneous injections of long-acting acylated GIP analog (acyl-GIP; 10nmol\/kg body weight) for 28 days. Body weight, food intake, whole-body composition were monitored throughout the study. Fasting blood glucose and intraperitoneal glucose tolerance test (ipGTT) were determined on day 21 of the study. Circulating lipid levels, lipoprotein profiles and atherosclerotic lesion size was assessed at the end of the study. Acyl-GIP effects on fat depots were determined by histology and transcriptomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Herein we found that treatment with acyl-GIP reduced dyslipidemia and atherogenesis in male LDLR-\/- mice. Acyl-GIP administration resulted in smaller adipocytes within the inguinal fat depot and RNAseq analysis of the latter revealed that acyl-GIP may improve dyslipidemia by directly modulating lipid metabolism in this fat depot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified an unanticipated efficacy of chronic GIPR agonism to improve dyslipidemia and cardiovascular disease independently of body weight loss, indicating that treatment with acyl-GIP may be a novel approach to alleviate cardiometabolic disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-023-01940-2","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T18:10:53Z","timestamp":1692295853000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease"],"prefix":"10.1186","volume":"22","author":[{"given":"Stephan","family":"Sachs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"G\u00f6tz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Finan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Feuchtinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"DiMarchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"D\u00f6ring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias H.","family":"Tsch\u00f6p","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo D.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna M.","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"issue":"1","key":"1940_CR1","doi-asserted-by":"publisher","first-page":"bqz029","DOI":"10.1210\/endocr\/bqz029","volume":"161","author":"JL Beaudry","year":"2020","unstructured":"Beaudry JL, Drucker DJ. 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He was a member of the Research Cluster Advisory Panel (ReCAP) of the Novo Nordisk Foundation between 2017 and 2019. He attended a scientific advisory board meeting of the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, in 2016. He received funding for his research projects from Novo Nordisk (2016\u20132020) and Sanofi-Aventis (2012\u20132019). He was a consultant for Bionorica SE (2013\u20132017), Menarini Ricerche S. p.A. (2016), and Bayer Pharma AG Berlin (2016). As former Director of the Helmholtz Diabetes Center and the Institute for Diabetes and Obesity at Helmholtz Zentrum M\u00fcnchen (2011\u20132018), and since 2018, as CEO of Helmholtz Zentrum M\u00fcnchen, he has been responsible for collaborations with a multitude of companies and institutions worldwide. In this capacity, he discussed potential projects with and has signed\/signs contracts for his institute(s) and for the staff for research funding and\/or collaborations with industry and academia worldwide, including, but not limited to, pharmaceutical corporations like Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medigene, Arbormed, BioSyngen, and others. In this role, he was\/is further responsible for commercial technology transfer activities of his institute(s), including diabetes-related patent portfolios of Helmholtz Zentrum M\u00fcnchen as, e.g., WO\/2016\/188,932 A2 or WO\/2017\/194,499 A1. M.H.T. confirms that to the best of his knowledge none of the above funding sources were involved in the preparation of this paper. S.S. is an employee of Cellarity, Inc and has stake-holder interests. The present work was carried out as an employee of the Helmholtz Zentrum Muenchen, HMGU.R.D.D. is a co-inventor on intellectual property owned by Indiana University and licensed to Novo Nordisk. He was previously employed by Novo Nordisk. B.F. is a current employee of Novo Nordisk.T.D.M. receives research funding from Novo Nordisk and the German Research Foundation (DFG TRR152 and TRR296), but these funds are unrelated to the here described work. T.D.M. has received speaking fees within the last 3 years from Novo Nordisk, Eli Lilly, AstraZeneca and Berlin Chemie AG. S.M.H. receives research funding from the German Research Foundation (FOR 5298) that is unrelated to the here described work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All procedures were approved by the local Animal Use and Care Committee and the local authorities of Upper Bavaria, Germany in accordance with European and German animal welfare regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have declared their consent for this publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"217"}}