Kaempferol reduces obesity, prevents intestinal inflammation, and modulates gut microbiota in high-fat diet mice

J Nutr Biochem. 2022 Jan:99:108840. doi: 10.1016/j.jnutbio.2021.108840. Epub 2021 Aug 20.

Abstract

Kaempferol, a flavonoid identified in a wide variety of dietary sources, has been reported to possess anti-obesity properties; however, its underlying mechanism was poorly understood. Chronic, low-grade gut inflammation and dysbacteria are proposed as underlying factors as well as novel treatment approaches for obesity-associated pathologies. This present study aims to investigate the benefits of experimental treatment with kaempferol on intestinal inflammation and gut microbial balance in animal model of obesity. High fat diet (HFD) was applied to C57BL/6J mice for 16 weeks, during which the supplement of kaempferol served as a variable. Clearly, HFD induced obesity, fat accumulation, glucose intolerance and adipose inflammation, the metabolic syndrome of which was the main finding. All these metabolic disorders can be alleviated through kaempferol supplementation. In addition, increased intestinal permeability, infiltration of immunocytes (macrophage, dendritic cells and neutrophils) and overexpression of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1) were also found in the HFD-induced mice. Kaempferol supplementation improved intestinal barrier integrity and inhibited gut inflammation, by reducing the activation of TLR4/NF-κB pathway. Furthermore, the characterization of the cecal microbiota by sequencing showed that kaempferol supplementation was able to counteract the dysbiosis associated to obesity. Our study delineated the multiple mechanism of action underlying the anti-obesity effect of kaempferol, and provide scientific evidence to support the development of kaempferol as a dietary supplement for obesity treatment.

Keywords: Gut microbiota; Intestinal inflammation; Kaempferol; Metabolic syndrome; Obesity; TLR4/NF-κB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / immunology
  • Animals
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Diet, High-Fat / adverse effects*
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Intestines / immunology*
  • Intestines / microbiology
  • Kaempferols / administration & dosage*
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy*
  • Obesity / immunology
  • Obesity / microbiology

Substances

  • Chemokine CCL2
  • Cytokines
  • Kaempferols
  • kaempferol