Differences in metabolic regulation among obesity phenotypes, specifically metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) women, may lead to varied responses to interventions, which could be elucidated through metabolomics. Therefore, this study aims to investigate the differences in metabolite profiles between MHO and MUO women and the changes following a lifestyle intervention. Serum samples from 36 MHO and 34 MUO women who participated in a lifestyle intervention for weight loss were analysed using untargeted proton nuclear magnetic resonance spectroscopy (¹H NMR) at baseline and 6 months post-intervention. Anthropometric, clinical, and dietary intake parameters were assessed at both time points. Both groups showed differential metabolite profiles at baseline and after six months. Seven metabolites, including trimethylamine-N-oxide (TMAO), arginine, ribose, aspartate, carnitine, choline, and tyrosine, significantly changed between groups post-intervention, which all showed a decreasing pattern in MHO. Significant reductions in body weight and body mass index (BMI) in the MUO correlated with changes in the carnitine and tyrosine levels. In conclusion, metabolite profiles differed significantly between MHO and MUO women before and after a lifestyle intervention. The changes in carnitine and tyrosine levels in MUO were correlated with weight loss, suggesting potential targets for therapeutic intervention.

Differences in metabolic regulation among obesity phenotypes, specifically metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) women, may lead to varied responses to interventions, which could be elucidated through metabolomics. Therefore, this study aims to investigate the differences in metabolite profiles between MHO and MUO women and the changes following a lifestyle intervention. Serum from 36 MHO and 34 MUO women, who participated in a lifestyle intervention for weight loss were analyzed using an untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) at baseline and 6 months post-intervention. Anthropometric, clinical and dietary intake parameters were assessed at both time points. Both groups showed differential metabolites profile at baseline and sixth month. Seven metabolites including trimethylamine-N-oxide (TMAO), arginine, ribose, aspartate, carnitine, choline and tyrosine significantly changed between group post-intervention, in which all showed a decreasing pattern in MHO. Significant reduction in body weight and BMI in the MUO correlated with changes in carnitine and tyrosine levels. In conclusion, metabolite profiles differed significantly between MHO and MUO women before and after a lifestyle intervention. Changes in carnitine and tyrosine levels in MUO correlated with weight loss, suggesting potential targets for therapeutic intervention.

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.