Polyphenols from Rhizopus oligosporus-fermented Amaranth Alleviate Insulin Resistance via IRS-1/PPARγ-Mediated GLUT4 Activation
Abstract
Abstract Insulin resistance underlies type 2 diabetes and metabolic syndrome, yet safe dietary interventions remain limited. In this study, solid-state fermentation of amaranth grain by Rhizopus oligosporus enriched its bioactive polyphenol profile, raising extraction yield from 2.83% to over 47%. After 3 days, antioxidant capacity and α-glucosidase/α-amylase inhibition peaked, with lipid-phase extracts exhibiting superior potency. In insulin-resistant HepG2 hepatocytes, the highest dose (400 µg/mL) increased glucose uptake and glycogen content to 260% and 427.23% of model-group levels, respectively, while restoring hexokinase and pyruvate kinase activities. Comparable phenotypic trends were also detected in 3T3-L1 adipocytes. Mechanistically, extracts concurrently activated the IRS-1/PI3K/Akt/GLUT4 axis in hepatocytes and the PPARγ/C-EBPα/GLUT4 pathway in adipocytes. Molecular docking further confirmed that quercetin and ferulic acid, the phenolics most enriched by fermentation, directly engage the PPARγ ligand-binding domain, providing structural evidence for their insulin-sensitizing actions. These findings establish R. oligosporus fermentation as a food-grade strategy to enhance amaranth's functional value for managing metabolic disorders.
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Evidence Hub reads this as a preprint, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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