{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:53:12Z","timestamp":1783569192147,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Clinical Medicine and Surgery of the Federico II University Hospital"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and\/or \u03b2-oxidation. Methods: According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma \u03b2-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid\/linoleic acid (C16:0\/C18:2 n6) and palmitoleic acid\/palmitic acid (C16:1\/C16:0) ratios, respectively. Results: Compared to baseline, mean \u00b1 SD DNL significantly decreased after the multifactorial diet (2.2 \u00b1 0.8 vs. 1.5 \u00b1 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 \u00b1 1.1 vs. 1.9 \u00b1 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 \u00b1 0.05 vs. 0.10 \u00b1 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma \u03b2-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). Conclusions: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416.<\/jats:p>","DOI":"10.3390\/nu14102178","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T03:16:55Z","timestamp":1653362215000},"page":"2178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-8002","authenticated-orcid":false,"given":"Giuseppina","family":"Costabile","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"Task Force on Microbiome Studies, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5862-3794","authenticated-orcid":false,"given":"Giuseppe","family":"Della Pepa","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-9036","authenticated-orcid":false,"given":"Dominic","family":"Salamone","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Luongo","sequence":"additional","affiliation":[{"name":"CNR\u2014Institute of Biostructures and Bioimaging, Naples, Via Mezzocannone 16, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5191-7669","authenticated-orcid":false,"given":"Daniele","family":"Naviglio","sequence":"additional","affiliation":[{"name":"Department of Chemical Science, Federico II University, Via Cintia 21, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-7645","authenticated-orcid":false,"given":"Valentina","family":"Brancato","sequence":"additional","affiliation":[{"name":"IRCCS Synlab SDN, Via Emanuele Gianturco, 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Cavaliere","sequence":"additional","affiliation":[{"name":"IRCCS Synlab SDN, Via Emanuele Gianturco, 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9734-7702","authenticated-orcid":false,"given":"Marco","family":"Salvatore","sequence":"additional","affiliation":[{"name":"IRCCS Synlab SDN, Via Emanuele Gianturco, 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cipriano","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Vitale","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Corrado","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Rivellese","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"Task Force on Microbiome Studies, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Annuzzi","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"Task Force on Microbiome Studies, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6549-4476","authenticated-orcid":false,"given":"Lutgarda","family":"Bozzetto","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"Task Force on Microbiome Studies, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-physiol-021115-105331","article-title":"Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease","volume":"78","author":"Haas","year":"2016","journal-title":"Annu. 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