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Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity.<\/jats:p>","DOI":"10.1111\/obr.12983","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T01:19:35Z","timestamp":1575854375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Pathophysiological connections between gallstone disease, insulin resistance, and obesity"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1658-0965","authenticated-orcid":false,"given":"V\u00edctor A.","family":"Cort\u00e9s","sequence":"first","affiliation":[{"name":"Department of Nutrition, Diabetes and Metabolism Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Barrera","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, School of Medicine Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Nervi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, School of Medicine Pontificia Universidad Cat\u00f3lica de Chile  Santiago 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