Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice

FASEB J. 2020 Sep;34(9):12053-12071. doi: 10.1096/fj.201903102RR. Epub 2020 Jul 30.

Abstract

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low-grade inflammation, and insulin resistance in mice fed high-fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD-induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo-treated mice to HFD-fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.

Keywords: fecal microbiota transplantation; flavonoids compound; intestinal microbiota; metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroidetes / growth & development*
  • Diet, High-Fat / adverse effects*
  • Firmicutes / growth & development*
  • Gastrointestinal Microbiome / drug effects*
  • Hesperidin / analogs & derivatives*
  • Hesperidin / pharmacology
  • Male
  • Mice
  • Obesity* / chemically induced
  • Obesity* / drug therapy
  • Obesity* / microbiology

Substances

  • Hesperidin
  • neohesperidin