{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T13:59:19Z","timestamp":1777039159497,"version":"3.51.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Limited data link manufactured sweeteners impact on metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the effects of manufactured sugars (L-glucose) compared to natural sugars (D-glucose) on phenotype, molecular and metabolic changes in mice models fed with either regular diet (RD) or high fat diet (HFD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6 mice fed 16-weeks with either RD; 70% carbohydrate or HFD; 60% fat, with or without additional glucose (Glu, at 18% w\/v) to drinking tap water at weeks 8\u201316; of either natural (D-Glu) or manufactured (L-Glu) sugars. Liver inflammation (ALT and AST serum levels, liver H&amp;amp;E histologic stains and cell viability profile by p-AKT), liver fibrosis [quantitated <jats:italic>\u03b1<\/jats:italic> smooth-muscle-actin (\u03b1SMA) by western blot and RT-PCR, Masson Trichrome staining (MTC) of liver tissue], liver lipid [steatosis stain by H&amp;amp;E, Adipose Differentiation-Related Protein (ADRP) lipid accumulation, serum and lipid peroxidation Malondialdehyde (MDA) markers by ELISA], glucose hemostasis (serum Glucose and C-peptide with HOMA-IR score calculation) and liver aspects [hepatic glucose transporter 2 (GLUT2), insulin receptor (IR) expressions and GYS2\/PYGL ratio] evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>D- and L-Glu supplementations propagate hepatocytes ballooning and steatosis in HFD-fed mice and were associated with \u03b1SMA down-expressions by 1.5-fold compared to the untreated group while showed an acceleration in liver fibrosis in the RD-fed mice. Lipid profile (Steatosis, ADRP and MDA) significantly increased in HFD-fed mice, both Glu supplementations (mainly the L-Glu) increased serum MDA while decreased ADRP. HOMA-IR score and IR significantly increased in HFD-fed mice, with further elevation in HOMA-IR score following Glu supplementations (mainly L-Glu). The increase in HOMA-IR negatively correlated with IR and Glut2 expressions. D- and L-Glu supplementations showed significant decrease of Glycogenesis (low GYS2\/PYGL ratio) and unchanged p-AKT pattern compared to their RD counterparts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicate an increase in rate of de-novo lipogenesis (DNL) in RD-fed mice (High carbohydrate diet) and liver fibrosis following additional sugar supplementations. In contrast, HFD-fed mice (with pre-existing high lipid profile) supplemented with sugar showed less liver fibrosis, because of reduced de-novo fatty acids synthesis and subsequently, the lipid oxidation pathways become dominated and induce the net results of lipid clearance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2024.1469952","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T15:18:54Z","timestamp":1734103134000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["High-fat diet mouse model receiving L-glucose supplementations propagates liver injury"],"prefix":"10.3389","volume":"11","author":[{"given":"Johnny","family":"Amer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athar","family":"Amleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Salhab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuval","family":"Kolodny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shira","family":"Yochelis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baker","family":"Saffouri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yossi","family":"Paltiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rifaat","family":"Safadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.3350\/cmh.2022.0365","article-title":"Global 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