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.