{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:21:02Z","timestamp":1777519262446,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK100425"],"award-info":[{"award-number":["R01DK100425"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK121710"],"award-info":[{"award-number":["R01DK121710"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK057521"],"award-info":[{"award-number":["P30DK057521"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are likely contributors to this epidemic. Among the involved dietary factors, excessive fructose consumption may be a key contributor. When fructose is consumed in large amounts, it can quickly produce many of the features of MetS both in humans and mice. The mechanisms by which fructose contributes to metabolic disease and its potential interactions with genetic factors in these processes remain uncertain. Here, we generated a small F2 genetic cohort of male mice derived from crossing fructose-sensitive and -resistant mouse strains to investigate the interrelationships between fructose-induced metabolic phenotypes and to identify hepatic transcriptional pathways that associate with these phenotypes. Our analysis indicates that the hepatic transcriptional pathways associated with fructose-induced hypertriglyceridemia and hyperinsulinemia are distinct from those that associate with fructose-mediated changes in body weight and liver triglyceride. These results suggest that multiple independent mechanisms and pathways may contribute to different aspects of fructose-induced metabolic disease.<\/jats:p>","DOI":"10.3390\/nu13103642","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T03:01:13Z","timestamp":1634698873000},"page":"3642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Ludivine","family":"Doridot","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah A.","family":"Hannou","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah A.","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4116-5904","authenticated-orcid":false,"given":"Wenxin","family":"Tong","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA"},{"name":"Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory S.","family":"McElroy","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8452-4845","authenticated-orcid":false,"given":"Alan J.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna I.","family":"Astapova","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-103X","authenticated-orcid":false,"given":"Mark A.","family":"Herman","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA"},{"name":"Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27705, USA"},{"name":"Division of Endocrinology and Metabolism and Nutrition, Duke University, Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0140-6736(09)61794-3","article-title":"The Metabolic Syndrome","volume":"375","author":"Eckel","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.2337\/dc12-0336","article-title":"Metabolic Syndrome and Risk of Cancer: A Systematic Review and Meta-Analysis","volume":"35","author":"Esposito","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41574-020-00452-3","article-title":"Metabolic Liver Disease\u2013What\u2019s in a Name?","volume":"17","author":"Herman","year":"2021","journal-title":"Nat. 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