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It has been shown that liver fat accumulates more readily in South Asian individuals, and this is thought to be a key driving factor contributing to the insulin resistance and diabetes in this population. However, the mechanisms underlying this phenomenon remain unclear. Understanding the role of de novo lipogenesis (DNL) in liver fat accumulation has been hampered by a lack of non-invasive techniques to quantify DNL-derived liver fat. We developed a method to quantify DNL-derived liver fat and used it in a proof-of-concept case\u2013control study, hypothesising that there would be greater liver fat contribution from DNL in South Asian individuals than in European individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of seven South Asian and six European participants, matched for age and BMI, underwent deuterium magnetic resonance scans at baseline and after 5 days of\n                      <jats:sup>2<\/jats:sup>\n                      H water enrichment, from which the fractional and absolute amounts of liver fat from DNL (DNL\n                      <jats:sub>MR<\/jats:sub>\n                      ) were calculated. Proton magnetic resonance spectroscopy (\n                      <jats:sup>1<\/jats:sup>\n                      H-MRS) and MRI were used to determine lipid quantity and composition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our method allowed precise quantification of\n                      <jats:sup>2<\/jats:sup>\n                      H-labelled liver lipids (intraclass correlation coefficient [ICC]&gt;0.956), which enabled us to accurately detect changes in liver fat due to DNL. Both fractional and absolute DNL\n                      <jats:sub>MR<\/jats:sub>\n                      were higher in South Asian participants than in European participants (both\n                      <jats:italic>p<\/jats:italic>\n                      =0.041). DNL\n                      <jats:sub>MR<\/jats:sub>\n                      correlated with liver fat content (fractional\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      =0.874, absolute\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      =0.888; both\n                      <jats:italic>p<\/jats:italic>\n                      =0.001), as well as the saturation ratio of both liver fat (fractional\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      =0.692, absolute\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      =0.748; both\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05) and visceral adipose tissue (fractional\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      =0.648, absolute\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      =0.708; both\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01). Liver fat content correlated with insulin resistance (HOMA-IR) (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      =0.659,\n                      <jats:italic>p<\/jats:italic>\n                      =0.014).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>DNL or related factors may play a pivotal role in driving the increased liver fat and risk of diabetes in South Asian individuals. The novel methodology used to quantify DNL provides a powerful tool for studying DNL-derived liver fat in human metabolic disorders including diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06876-2","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:36:13Z","timestamp":1791297373000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deuterium metabolic imaging reveals greater liver fat contribution from lipogenesis in South Asian men than European men: a potential mechanism underlying elevated type 2 diabetes risk"],"prefix":"10.1007","author":[{"given":"Mueed","family":"Azhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieniean","family":"Worsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn M. J. 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We are grateful to everyone at RAPID Biomedical GmbH (Rimpar, Germany) for custom design of the excellent\n                      2\n                      H\/\n                      1\n                      H coil. We would like to thank staff at the NIHR Core Biochemistry Assay Laboratory, Cambridge Biomedical Research Centre, for performing all of the assays other than the HbA\n                      1c\n                      , for which we acknowledge the support and analytical services of Cambridge University Hospitals NHS Foundation Trust Laboratory Research Services and clinical laboratories.","order":1,"name":"Ethics","label":"Acknowledgements","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Anonymised datasets from participants who consented to data sharing are available from the corresponding author following approval of the study team. Any data shared with external researchers will be protected by data-sharing agreements to ensure appropriate use, prevent unauthorised sharing, and ensure proper acknowledgement of the research team and funders.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This work was funded by the Medical Research Council (MRC; MR\/V011758\/1 to AS) and the study used infrastructure supported by the National Institute for Health and Care Research (NIHR)\u00a0Cambridge Clinical Research Facility; the NIHR\u00a0Cambridge Biomedical Centre (BRC 1215 20014, NIHR203312); the Wellcome Trust (208363\/Z\/17\/Z, 226800\/Z\/22\/Z); and the MRC (MC_UU_00014, MC_UU_00039). The GC-MS analysis was funded by the British Heart Foundation (Fellowship FS\/SBSRF\/21\/31013 to LH). KMB is currently in receipt of a Hans Fischer Senior Fellowship at the Technical University Munich. NGF acknowledges funding support from the MRC Epidemiology Unit (MC_UU_00006\/3) and the NIHR Cambridge Biomedical Research Centre, and an NIHR Senior Investigator Award (NIHR202397). DBS is supported by the Wellcome Trust (WT 219417), MRC (MR\/X00970X\/1), NIHR Cambridge Biomedical Research Centre and NIHR Rare Disease Translational Research Collaboration. AS gratefully acknowledges support from the NIHR Cambridge Clinical Research Facility. This is a summary of independent research funded by the MRC and carried out at the NIHR Cambridge Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Medical Research Council, the NIHR or the Department of Health and Social Care.","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","label":"Authors\u2019 relationships and activities","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"AS conceived the study. SRW, PB, MV, LW, LH, DBS and AS designed the study. MA, JW, MOM, KC, MF, RDJ, SK and SJ acquired the data. MA, JW, KMJH, AB, ED, KC, PB and AS analysed the data. EDLR, ED, GJK, KMB, KKC, NGF, LH, DBS and AS interpreted the data. MA, GJK, PB and AS drafted the manuscript. All authors reviewed the manuscript and approved the final version. AS is responsible for the integrity of the work as a whole.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}