Red Wine High-Molecular-Weight Polyphenolic Complex Ameliorates High-Fat Diet-Induced Metabolic Dysregulation and Perturbation in Gut Microbiota in Mice

Red wine polyphenolic complexes have attracted increasing attention as potential modulators of human metabolic disease risk. Our previous study discovered that red wine high-molecular-weight polymeric polyphenolic complexes (HPPCs) could inhibit key metabolic syndrome-associated enzymes and favorably modulate human gut microbiota (GM) in simulated colonic fermentation assay in vitro. In this work, the efficacy of HPPC supplementation (150 and 300 mg/kg/day, respectively) against high-fat diet (HFD)-induced metabolic disturbance in mice was investigated. HPPCs effectively attenuated HFD-induced obesity, insulin resistance, and lipid and glucose metabolic dysregulation and ameliorated inflammatory response and hepatic and colonic damage. It also improved the relative abundance of Bacteroidetes and Firmicutes, consistent with an anti-obesity phenotype. The favorable modulation of GM was further supported by improvement in the profile of fecal short-chain fatty acids. The higher dosage generally had a better performance in these effects than the low dosage. Moreover, serum metabolite profiling and pathway enrichment analysis revealed that HPPCs significantly modulated vitamin B metabolism-associated pathways and identified N-acetylneuraminic acid and 2-methylbutyroylcarnitine as potential biomarkers of the favorable effect on HFD-induced metabolic dysregulation. These findings highlight that dietary supplementation with red wine HPPCs is a promising strategy for the management of weight gain and metabolic dysregulation associated with HFD.