The effects of high‐fat diet and metformin on urinary metabolites in diabetes and prediabetes rat models

Abstract

High-fat diet (HFD) interferes with the dietary plan of patients with type 2 diabetes mellitus (T2DM). However, many diabetes patients consume food with higher fat content for a better taste bud experience. In this study, we examined the effect of HFD on rats at the early onset of diabetes and prediabetes by supplementing their feed with palm olein oil to provide a fat content representing 39% of total calorie intake. Urinary profile generated from liquid chromatography-mass spectrometry analysis was used to construct the orthogonal partial least squares discriminant analysis (OPLS-DA) score plots. The data provide insights into the physiological state of an organism. Healthy rats fed with normal chow (NC) and HFD cannot be distinguished by their urinary metabolite profiles, whereas diabetic and prediabetic rats showed a clear separation in OPLS-DA profile between the two diets, indicating a change in their physiological state. Metformin treatment altered the metabolomics profiles of diabetic rats and lowered their blood sugar levels. For prediabetic rats, metformin treatment on both NC-and HFD-fed rats not only reduced their blood sugar levels to normal but also altered the urinary metabolite profile to be more like healthy rats. The use of metformin is therefore beneficial at the prediabetes stage.

Characterization and Comparison of the Divergent Metabolic Consequences of High-Sugar and High-Fat Diets in Male Wistar Rats

“…Of relevance to the present study are other published works where multivariate data analyses have been used to improve our understanding of the differences between various rodent metabolic models, for example, by characterising the different metabolic profiles of lean, high-fat diet (HFD)-fed and HFD/streptozotocin (STZ)-induced T2D rats ( Chen et al, 2021 ) or of HFD/STZ-induced T2D vs. STZ-induced type I diabetic rats ( Mediani et al, 2018 ). The impact of diabetic status on the metabolic response to HFD has also been explored using this methodology ( Lee et al, 2021 ). In addition, Letsinger et al (2020) demonstrated how a high-fat/high-sugar diet differentially affects the gut metabolome between male and female mice, which is of particular importance given the predominance of male rodent use in animal dietary studies and the lack of studies comparing the responses of male and female rodents to obesogenic feeding, as identified in our literature survey.…”

Metabolomic Approaches to Investigate the Effect of Metformin: An Overview

“…Mediani et al [ 82 ] performed NMR-based untargeted metabolomic analysis to understand the biochemical changes in streptozotocin (STZ)-induced, normal-, and obese-diabetic rates with metformin treatment (150 mg/kg/day), suggesting that metformin may provide better improvement for T2DM complications and insulin sensitivity for obese diabetes rather than normal diabetes. Lee et al [ 83 ] also carried out an LC-MS-based untargeted urinary metabolomics study in diabetes and prediabetes rat models, revealing the alteration of urine metabolomes. For prediabetic rats, metformin treatment (250 mg/kg/day) altered the urinary metabolite profile to be more like that of healthy rats ( Table 3 ).…”

Investigation of the Chemical Composition, Antihyperglycemic and Antilipidemic Effects of Bassia eriophora and Its Derived Constituent, Umbelliferone on High-Fat Diet and Streptozotocin-Induced Diabetic Rats

“…Therefore, the use of STZ + HFD has been reported to impair the secretions of insulin, which causes hyperglycemia and dyslipidemia, amongst other disorders [ 42 , 43 , 44 ]. Our study showed significant increases in blood glucose on the third day of STZ injection in rats fed with HFD.…”