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The aims of this study were to investigate whether VSG leads to weight\u2010loss independent improvements in liver steatosis in mice with diet\u2010induced obesity (DIO); and to metabolically and transcriptomically profile hepatic changes in mice undergoing VSG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice with DIO were treated with VSG, sham surgery with subsequent food restriction to weight\u2010match to the VSG group (Sham\u2010WM), or sham surgery with return to unrestricted diet (Sham\u2010Ad lib). Hepatic steatosis, glucose tolerance, insulin and glucagon resistance, and hepatic transcriptomics were investigated at the end of the study period and treatment groups were compared with mice undergoing sham surgery only (Sham\u2010Ad lib).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>VSG led to much greater improvement in liver steatosis than Sham\u2010WM (liver triglyceride mg\/mg 2.5\u2009\u00b1\u20090.1, 2.1\u2009\u00b1\u20090.2, 1.6\u2009\u00b1\u20090.1 for Sham\u2010AL, Sham\u2010WM and VSG respectively; <jats:italic>p<\/jats:italic>\u2009=\u20090.003). Homeostatic model assessment of insulin resistance was improved following VSG only (51.2\u2009\u00b1\u20098.8, 36.3\u2009\u00b1\u20095.3, 22.3\u2009\u00b1\u20096.1 for Sham\u2010AL, Sham\u2010WM and VSG respectively; <jats:italic>p<\/jats:italic>\u2009=\u20090.03). The glucagon\u2010alanine index, a measure of glucagon resistance, fell with VSG but was significantly increased in Sham\u2010WM (9.8\u2009\u00b1\u20091.7, 25.8\u2009\u00b1\u20094.6 and 5.2\u2009\u00b1\u20091.2 in Sham Ad\u2010lib, Sham\u2010WM and VSG respectively; <jats:italic>p<\/jats:italic>\u2009=\u20090.0003). Genes downstream of glucagon receptor signalling which govern fatty acid synthesis (<jats:italic>Acaca, Acacb, Me1, Acly, Fasn<\/jats:italic> and <jats:italic>Elovl6<\/jats:italic>) were downregulated following VSG but upregulated in Sham\u2010WM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Changes in glucagon sensitivity may contribute to weight\u2010loss independent improvements in hepatic steatosis following VSG.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15614","type":"journal-article","created":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T06:59:54Z","timestamp":1684565994000},"page":"1890-1900","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sleeve gastrectomy causes weight\u2010loss independent improvements in hepatic steatosis"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-6972","authenticated-orcid":false,"given":"Emma Rose","family":"McGlone","sequence":"first","affiliation":[{"name":"Department of Surgery and Cancer Imperial College London  London UK"},{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Siebert","sequence":"additional","affiliation":[{"name":"Centre de Recherche sur l'Inflammation, UMRS1149, Inserm, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Dore","sequence":"additional","affiliation":[{"name":"Genomics Facility MRC London Institute of Medical Sciences (LMS), Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-0687","authenticated-orcid":false,"given":"David C. D.","family":"Hope","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iona","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryn","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-9736","authenticated-orcid":false,"given":"Bernard","family":"Khoo","sequence":"additional","affiliation":[{"name":"Division of Medicine University College London, Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Goldin","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-1830","authenticated-orcid":false,"given":"Dave","family":"Carling","sequence":"additional","affiliation":[{"name":"Cellular Stress Group MRC LMS, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Le\u00a0Gall","sequence":"additional","affiliation":[{"name":"Centre de Recherche sur l'Inflammation, UMRS1149, Inserm, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-3432","authenticated-orcid":false,"given":"Tricia M\u2010M.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.05.064"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.005"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soard.2018.12.002"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.10.017"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.06.006"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soard.2019.09.060"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-021-05412-y"},{"key":"e_1_2_12_11_1","unstructured":"ASMBS.Estimate of bariatric surgery numbers 2011\u20132020.2022. 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