D-allulose attenuates dyslipidemia, oxidative stress, and inflammation in high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in rats.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a diet-related metabolic disorder characterized by hepatic lipid accumulation, dyslipidemia, insulin resistance, oxidative stress, and chronic inflammation, highlighting the need for safe nutritional interventions. Aim: This study evaluated the antihyperlipidemic, antioxidant, and anti-inflammatory effects of D-allulose, alone or in combination with dorsomorphin, in a high-fat diet (HFD)-induced rat model of Metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Forty-eight male Wistar rats were allocated to a control diet group, an HFD group, or an HFD group treated orally with D-allulose (0.3 or 0.6 g/kg) with or without dorsomorphin (0.2 mg/kg) orally for 12 weeks. Omnibus 𝑝-values for the 22 biochemical endpoints were subjected to a retrospective Benjamini-Hochberg false-discovery-rate sensitivity analysis. Results: HFD feeding induced weight gain, dyslipidemia, hepatic injury, oxidative stress, inflammation, and hyperinsulinemia. D-allulose dose-dependently ameliorated these disturbances, reducing atherogenic lipids, lipid peroxidation, inflammatory cytokines, and insulin while improving antioxidant status. Notably, TG decreased from 164.51 mg dL Conclusion: The combination groups generally matched or outperformed D-allulose alone across several biochemical and histological endpoints. However, because dorsomorphin is a non-selective AMPK/BMP inhibitor and AMPK activity was not directly measured, these findings do not establish AMPK's mechanistic involvement. Overall, D-allulose shows promising protective impacts as a bioactive ingredient for obesity-related metabolic disorders.