D-allulose attenuates dyslipidemia, oxidative stress, and inflammation in high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in rats.
- 1Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia.
- 2Department of Food Science and Human Nutrition, College of Agriculture and Food, Qassim University, Buraydah, Saudi Arabia.
Abstract
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. 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). 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. 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-1 in HFD rats to 113.52 and 99.43 mg dL-1 with low- and high-dose D-allulose, respectively, while LDL-C decreased from 86.45 to 53.19 and 49.24 mg dL-1; HDL-C remained unchanged. D-allulose also attenuated HFD-induced hepatic steatosis, degeneration, necrosis, inflammation, and early fibrosis, and this histological protection was maintained or enhanced by dorsomorphin co-administration. A retrospective FDR sensitivity analysis supported the principal lipid, antioxidant, inflammatory, and insulin findings, whereas the ALT and FBG findings did not remain significant and were considered exploratory. 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.
Related
- Phenolic-Rich Aronia melanocarpa (cv. Nero) Extract Attenuates Doxorubicin-Induced Nephrotoxicity Associated with Reduced Oxidative Stress, Inflammation, and Endoplasmic Reticulum Stress
- Theranekron Attenuates Inflammation, Oxidative Stress Index, and Apoptosis in Lipopolysaccharide‐Induced Cardiovascular Toxicity: Association With Hypoxia‐Inducible Factor‐1 Alpha‐Related Gene Expression
- SMTP-44D Attenuates Renal Inflammatory/Oxidative Dysfunction in a Mouse Model of Ischemia-Reperfusion-Induced Acute Kidney Injury.
- Cassia fistula L. Fruit Extract Attenuates Renal and Cardiac Toxicities by Reducing Oxidative Stress and Inflammation in Fludrocortisone Acetate‐Treated Long Evans Rats
- Thymol attenuates carboplatin-induced nephrotoxicity in male rats by suppressing oxidative stress and NF-κB-mediated inflammation: A biochemical and histopathological study
BibTeX
@article{almutairi2026dallulose,
title = {{D-allulose attenuates dyslipidemia, oxidative stress, and inflammation in high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in rats.}},
author = {Sami O Almutairi and Abu ElGasim A Yagoub and Hassan Barakat},
journal = {Frontiers in nutrition},
year = {2026},
month = oct,
doi = {10.3389/fnut.2026.1982241},
url = {https://europepmc.org/article/MED/42952798},
note = {CC BY},
}
RIS
TY - JOUR
TI - D-allulose attenuates dyslipidemia, oxidative stress, and inflammation in high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in rats.
AU - Sami O Almutairi
AU - Abu ElGasim A Yagoub
AU - Hassan Barakat
PY - 2026
DA - 2026/10/14
JO - Frontiers in nutrition
DO - 10.3389/fnut.2026.1982241
UR - https://europepmc.org/article/MED/42952798
AB - 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. 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). 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. 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-1 in HFD rats to 113.52 and 99.43 mg dL-1 with low- and high-dose D-allulose, respectively, while LDL-C decreased from 86.45 to 53.19 and 49.24 mg dL-1; HDL-C remained unchanged. D-allulose also attenuated HFD-induced hepatic steatosis, degeneration, necrosis, inflammation, and early fibrosis, and this histological protection was maintained or enhanced by dorsomorphin co-administration. A retrospective FDR sensitivity analysis supported the principal lipid, antioxidant, inflammatory, and insulin findings, whereas the ALT and FBG findings did not remain significant and were considered exploratory. 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.
SN - 2296-861X
ER -