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Diabetology","award":["GIFT-2020"],"award-info":[{"award-number":["GIFT-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: In MASLD (formerly called NAFLD) mouse models, oversupply of dietary fat and sugar is more lipogenic than either nutrient alone. Fatty acids suppress de novo lipogenesis (DNL) from sugars, while DNL inhibits fatty acid oxidation. How such factors interact to impact hepatic triglyceride levels are incompletely understood. Methods: Using deuterated water, we measured DNL in mice fed 18-weeks with standard chow (SC), SC supplemented with 55\/45-fructose\/glucose in the drinking water at 30% (w\/v) (HS), high-fat chow (HF), and HF with HS supplementation (HFHS). Liver glycogen levels and its sources were also measured. For HS and HFHS mice, pentose phosphate (PP) fluxes and fructose contributions to DNL and glycogen were measured using [U-13C]fructose. Results: The lipogenic diets caused significantly higher liver triglyceride levels compared to SC. DNL rates were suppressed in HF compared to SC and were partially restored in HFHS but supplied a minority of the additional triglyceride in HFHS compared to HF. Fructose contributed a significantly greater fraction of newly synthesized saturated fatty acids compared to oleic acid in both HS and HFHS. Glycogen levels were not different between diets, but significant differences in Direct and Indirect pathway contributions to glycogen synthesis were found. PP fluxes were similar in HS and HFHS mice and were insufficient to account for DNL reducing equivalents. Conclusions: Despite amplifying the lipogenic effects of fat, the fact that sugar-activated DNL per se barely contributes suggests that its role is likely more relevant in the inhibition of fatty acid oxidation. Fructose promotes lipogenesis of saturated over unsaturated fatty acids and contributes to maintenance of glycogen levels. PP fluxes associated with sugar conversion to fat account for a minor fraction of DNL reducing equivalents.<\/jats:p>","DOI":"10.3390\/nu16142186","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T13:22:36Z","timestamp":1720531356000},"page":"2186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Effects of Long-Term High Fat and\/or High Sugar Feeding on Sources of Postprandial Hepatic Glycogen and Triglyceride Synthesis in Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0892-7164","authenticated-orcid":false,"given":"Ana","family":"Reis-Costa","sequence":"first","affiliation":[{"name":"PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC-UC), Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"Grupo de Estudos de Investiga\u00e7\u00e3o Fundamental e Translacional (GIFT) da Sociedade Portuguesa de Diabetologia, 1250-198 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Getachew D.","family":"Belew","sequence":"additional","affiliation":[{"name":"PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC-UC), Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2589-2212","authenticated-orcid":false,"given":"Ivan","family":"Viegas","sequence":"additional","affiliation":[{"name":"Centre for Functional Ecology (CFE), TERRA Associate Laboratory, Department of Life Sciences, University of Coimbra, 3030-790 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-1259","authenticated-orcid":false,"given":"Ludgero C.","family":"Tavares","sequence":"additional","affiliation":[{"name":"Vasco da Gama Research Center (CIVG), University School Vasco da Gama, 3020-210 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8236-5411","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Meneses","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-4540","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Patr\u00edcio","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"},{"name":"National Research Council (CNR), Institute of Clinical Physiology (IFC), 56124 Pisa, Italy"},{"name":"Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-1651","authenticated-orcid":false,"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Institute of Clinical Physiology (IFC), 56124 Pisa, Italy"},{"name":"Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-0275","authenticated-orcid":false,"given":"Maria Paula","family":"Macedo","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"},{"name":"APDP-Diabetes Portugal Education and Research Center (APDP-ERC), 1250-203 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Jones","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC-UC), Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"},{"name":"Grupo de Estudos de Investiga\u00e7\u00e3o Fundamental e Translacional (GIFT) da Sociedade Portuguesa de Diabetologia, 1250-198 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. 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