Sugar substitutes that maintain the homeostasis of glucose, lipid, and protein metabolism are important for nutritional intervention in type 2 diabetes mellitus (T2DM). However, the specific metabolic effects remain unclear. The aim of this study was to systematically compare the effects of four common sugar substitutes on a high-fat diet (HFD) combined with a streptozotocin (STZ)-induced T2DM mouse model from the perspective of hepatic glucose, lipid, and protein metabolism. In this study, based on the establishment of a T2DM mouse model induced by an HFD combined with STZ and nontargeted metabolomics, the effects of four sugar substitutes on regulating and improving sugar, lipid, and protein metabolism were systematically evaluated. The results showed that mogroside V (MOG), stevioside (ST), and erythritol (ERT) enhanced protein synthesis via the mammalian target of the rapamycin/p-P70S6K pathway. MOG and ST also improved glucose and lipid metabolism by activating the phosphor-AMP-activated protein kinase (p-AMPK) pathway and upregulating peroxisome proliferator-activated receptor alpha/carnitine palmitoyltransferase 1. Sucralose primarily improves lipid metabolism by downregulating sterol regulatory element-binding protein 1, whereas ERT increases lipid droplet accumulation in the liver. These findings provide a foundation for the application of sugar substitutes in T2DM nutritional interventions.
Keywords: Erythritol; Glucose; Lipid and protein metabolism; Mogroside V; Stevioside; Sucralose; Sugar substitute; T2DM.
Copyright © 2025 Elsevier Ltd. All rights reserved.