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Area of Science:

  • Neuroscience
  • Microbiology
  • Metabolomics

Background:

  • Obesity induced by high-fat diets (HFD) is linked to neuroinflammation and cognitive impairment.
  • The gut microbiome and its metabolites play a crucial role in the gut-brain axis.
  • Proanthocyanidins (PAs) are bioactive compounds with potential anti-inflammatory properties.

Purpose of the Study:

  • To investigate the effects of proanthocyanidins (PAs) on neuroinflammation in high-fat diet (HFD)-induced obese mice.
  • To explore the modulation of colonic microflora and their metabolites by PAs.
  • To assess the impact of PAs on cognitive function in obese mice.

Main Methods:

  • Thirty male C57BL/6J mice were divided into control, HFD, and PA-treated HFD groups.
  • Mice were fed respective diets for 8 weeks, followed by PA or saline administration.
  • Evaluations included gut microbiota analysis, non-targeted metabolomics, gene expression for neuroinflammation, and Morris water maze for cognitive function.

Main Results:

  • PA treatment significantly reduced body weight, hepatic fat accumulation, and inflammation markers in HFD mice.
  • PAs decreased hippocampal pro-inflammatory cytokines (IL-1β, TNF-α) and lipopolysaccharide, while increasing Sirt1 and FGF21.
  • PA administration altered colonic microbiota composition (e.g., increased Lactobacillus, Akkermansia) and shifted metabolite profiles (e.g., steroid hormone biosynthesis, tryptophan metabolism), correlating with reduced neuroinflammation.

Conclusions:

  • Proanthocyanidins (PAs) effectively modulate colonic microflora and metabolites, thereby mitigating neuroinflammation in HFD-induced obese mice.
  • PAs demonstrate a protective effect against cognitive decline associated with HFD-induced obesity.
  • These findings suggest PAs as a potential therapeutic strategy for managing obesity-related neurological complications.