Anti-diabetic effects of allulose in diet-induced obese mice via regulation of mrna expression and alteration of the microbiome composition

Allulose has been reported to serve as an anti-obesity and anti-diabetic food component; however, its molecular mechanism is not yet completely understood. This study aims to elucidate the mechanisms of action for allulose in obesity-induced type 2 diabetes mellitus (T2DM), by analyzing the transcriptional and microbial populations of diet-induced obese mice. Thirty-six C57BL/6J mice were divided into four groups, fed with a normal diet (ND), a high-fat diet (HFD), a HFD supplemented with 5% erythritol, or a HFD supplemented with 5% allulose for 16 weeks, in a pair-fed manner. The allulose supplement reduced obesity and comorbidities, including inflammation and hepatic steatosis, and changed the microbial community in HFD-induced obese mice. Allulose attenuated obesity-mediated inflammation, by downregulating mRNA levels of inflammatory response components in the liver, leads to decreased plasma pro-inflammatory marker levels. Allulose suppressed glucose and lipid metabolism-regulating enzyme activities, ameliorating hepatic steatosis and improving dyslipidemia. Allulose improved fasting blood glucose (FBG), plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and the area under the curve (AUC) for the intraperitoneal glucose tolerance test (IPGTT), as well as hepatic lipid levels. Our findings suggested that allulose reduced HFD-induced obesity and improved T2DM by altering mRNA expression and the microbiome community.