Leptin improves intestinal flora dysfunction in mice with high-fat diet-induced obesity

J Int Med Res. 2020 Jun;48(6):300060520920062. doi: 10.1177/0300060520920062.

Abstract

Objective: This study investigated the effects of leptin on intestinal flora and inflammation in mice with high-fat diet (HFD)-induced obesity.

Methods: Mice were fed an HFD for 8 weeks; some were concurrently administered oral leptin for 4 weeks. Pathological changes in adipose tissue were detected using hematoxylin-eosin staining; endotoxin content in adipose tissue was measured by enzyme-linked immunosorbent assay. Intestinal flora were characterized by 16S bacterial rDNA sequencing. Levels of Toll-like receptor 4 (TLR4), nuclear factor-κB inhibitor α (IκB-α), and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by western blotting.

Results: Mice in the HFD group exhibited weight gain, elevated endotoxin content, and adipocyte hypertrophy, compared with the non-obese control group. Moreover, abundance of bacteria in the Bacteroides genus and community diversity were both reduced in the HFD group; reductions also were observed at corresponding phylum, class, and order levels. Levels of TLR4, IκB-α, and p-JNK were also elevated in the HFD group. Compared with the model group, leptin administration reduced the weight gain and endotoxin content, while increasing Bacteroides abundance and community diversity; it also reduced the levels of TLR4, IκB-α, and p-JNK.

Conclusion: Leptin administration improved intestinal flora dysfunction and inflammation in mice with HFD-induced obesity.

Keywords: Bacteroides; Leptin; Toll-like receptor 4; adipose tissue; c-Jun N-terminal kinase; high-fat diet; inflammation; intestinal flora; nuclear factor-κB inhibitor α; obesity.

MeSH terms

  • Adipose Tissue / chemistry
  • Adipose Tissue / immunology
  • Adipose Tissue / pathology
  • Administration, Oral
  • Animals
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Endotoxins / analysis
  • Endotoxins / immunology
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / microbiology
  • Inflammation / pathology
  • Leptin / administration & dosage*
  • Male
  • Mice
  • Obesity / drug therapy*
  • Obesity / immunology
  • Obesity / microbiology
  • Obesity / pathology

Substances

  • Endotoxins
  • Leptin