Metabolomic Insights on Obesity and Diabetes from Feeding Diets Varying in Carbohydrate-Fat Ratios in Zucker Diabetic Fatty (ZDF) and Lean Zucker (Z_lean) Rats.

Authors

Mohd Naeem Mohd Nawi, Ranina Radzi, Azizan Ali, Siti Zubaidah Che Lem, Azlina Zulkapli, Ezarul Faradianna Lokman, Mansor Fazliana, Fatin Saparuddin, Norazlan Mohmad Misnan, Sreelakshmi Sankara Narayanan, Karuthan Chinna, Mohd Fairulnizal Md Noh, Zulfitri Azuan Mat Daud, Tilakavati Karupaiah

Published in

International journal of molecular sciences. Volume 27. Issue 15. Aug 04, 2026. Epub Aug 04, 2026.

Abstract

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-fat permutations in Zucker diabetic fatty (ZDF) and Zucker lean (Z_lean) 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 Z_lean 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-β-D-glucose, 2-hydroxyvalerate, acetate, 3-aminoisobutyrate, 3-hydroxybutyrate, carnitine, choline, citrate, creatine, lactate, and N-methylhydantoin) (all p < 0.05) which remained significant even after false discovery rate (FDR) correction. Majorly elevated metabolites in both ZDF and Z_lean rats were 3-hydroxybutyrate, N-methylhydantoin, 3-aminoisobutyrate, and carnitine, indicating dietary influences independent of diabetes status. Conversely, citrate and 1,6-anhydro-β-D-glucose levels showed distinct patterns across the groups, with Z_lean 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 Z_lean rats, while metformin treatment generally improved metabolic profiles.

PMID:
42589668
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.