{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:14:08Z","timestamp":1786115648785,"version":"build-2736575974"},"reference-count":111,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013885","name":"Ministry of Health Malaysia","doi-asserted-by":"crossref","award":["NMRR-20-413-5300"],"award-info":[{"award-number":["NMRR-20-413-5300"]}],"id":[{"id":"10.13039\/501100013885","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>In population health the highly cited Atherosclerosis Risk in Communities study indicated a U-shaped association between carbohydrate intake and mortality, whilst the Prospective Urban Rural Epidemiology study linked higher fat intake to lower mortality risks. The Malaysia Lipid Study reported high-fat and high-carbohydrate dietary patterns were associated with increased cardiometabolic risks, including insulin resistance and small dense LDL particles generation. This animal model study therefore was purposely designed to evaluate metabolic outcomes of carbohydrate\u2013fat permutations in Zucker diabetic fatty (ZDF) and Zucker lean (Zlean) rats by using 1H Nuclear Magnetic Resonance (NMR) metabolomics. Twenty-four ZDF rats were randomly divided into four groups (n = 6 per group): control (standard diet), Diet A (54%-energy carbohydrate, 32%-energy fat, 14%-energy protein) mimicking a recommended adult Malaysian diet, Diet B (49%-energy carbohydrate, 37%-energy fat, 14%-energy protein) mimicking a low-carbohydrate, moderate high-fat diet, and metformin treatment (100 mg\/kg), which effectively represents a 5%-energy exchange in isocaloric meals. An additional six Zlean were given Diet A (n = 3) and Diet B (n = 3). The intervention lasted eight weeks. Using log-transformed data, analysis of variance (ANOVA) revealed significant differences between the groups for eleven metabolites (1,6-anhydro-\u03b2-D-glucose, 2-hydroxyvalerate, acetate, 3-aminoisobutyrate, 3-hydroxybutyrate, carnitine, choline, citrate, creatine, lactate, and N-methylhydantoin) (all p &lt; 0.05) which remained significant even after false discovery rate (FDR) correction. Majorly elevated metabolites in both ZDF and Zlean rats were 3-hydroxybutyrate, N-methylhydantoin, 3-aminoisobutyrate, and carnitine, indicating dietary influences independent of diabetes status. Conversely, citrate and 1,6-anhydro-\u03b2-D-glucose levels showed distinct patterns across the groups, with Zlean rats exhibiting lower levels and ZDF rats showing higher levels compared to healthy controls, suggesting potential genetic or physiological influences. Other metabolites such as creatine, acetate, choline and 2-hydroxyvalerate showed varied trends, highlighting metabolic complexities. Compared to the control group, metformin treatment generally resulted in lower levels of metabolites, except for acetate, which was higher, indicating improved insulin sensitivity. The findings indicated moderate high-fat diets may exacerbate metabolic disturbances as seen in both ZDF and Zlean rats, while metformin treatment generally improved metabolic profiles.<\/jats:p>","DOI":"10.3390\/ijms27157017","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:30:52Z","timestamp":1785861052000},"page":"7017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomic Insights on Obesity and Diabetes from Feeding Diets Varying in Carbohydrate\u2013Fat Ratios in Zucker Diabetic Fatty (ZDF) and Lean Zucker (Zlean) Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-017X","authenticated-orcid":false,"given":"Mohd Naeem","family":"Mohd Nawi","sequence":"first","affiliation":[{"name":"Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranina","family":"Radzi","sequence":"additional","affiliation":[{"name":"Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azizan","family":"Ali","sequence":"additional","affiliation":[{"name":"Good Laboratory Practice Section, Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Kuala Lumpur 50588, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Zubaidah","family":"Che Lem","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Unit, Special Resource Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Kuala Lumpur 50588, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azlina","family":"Zulkapli","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Unit, Special Resource Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Kuala Lumpur 50588, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezarul Faradianna","family":"Lokman","sequence":"additional","affiliation":[{"name":"Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansor","family":"Fazliana","sequence":"additional","affiliation":[{"name":"Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"},{"name":"Manager\u2019s Office, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5024-472X","authenticated-orcid":false,"given":"Fatin","family":"Saparuddin","sequence":"additional","affiliation":[{"name":"Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-9543","authenticated-orcid":false,"given":"Norazlan","family":"Mohmad Misnan","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreelakshmi Sankara","family":"Narayanan","sequence":"additional","affiliation":[{"name":"School of Biosciences, Faculty of Health and Medical Sciences, Taylor\u2019s University, Subang Jaya 47500, Malaysia"},{"name":"Centre for Active Living, Taylor\u2019s University, Subang Jaya 47500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karuthan","family":"Chinna","sequence":"additional","affiliation":[{"name":"Institute of Research, Development and Innovation, IMU University, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6960-0774","authenticated-orcid":false,"given":"Mohd Fairulnizal","family":"Md Noh","sequence":"additional","affiliation":[{"name":"Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4017-107X","authenticated-orcid":false,"given":"Zulfitri Azuan","family":"Mat Daud","sequence":"additional","affiliation":[{"name":"Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5808-8074","authenticated-orcid":false,"given":"Tilakavati","family":"Karupaiah","sequence":"additional","affiliation":[{"name":"Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2025). 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