Microbiome Transfer Partly Overrides Lack of IL-1RI Signaling to Alter Hepatic but not Adipose Tissue Phenotype and Lipid Handling following a High-Fat Diet Challenge

Mol Nutr Food Res. 2021 Jan;65(1):e2000202. doi: 10.1002/mnfr.202000202. Epub 2020 Jul 12.

Abstract

Scope: IL-1RI-mediated inflammatory signaling alters metabolic tissue responses to dietary challenges (e.g., high-fat diet [HFD]). Recent work suggests that metabolic phenotype is transferrable between mice in a shared living environment (i.e., co-housing) due to gut microbiome exchange. The authors examine whether the metabolic phenotype of IL-1RI-/- mice fed HFD or low-fat diet (LFD) could be transferred to wild-type (WT) mice through gut microbiome exchange facilitated by co-housing.

Methods and results: Male WT (C57BL/J6) and IL-1RI-/- mice are fed HFD (45% kcal) or LFD (10% kcal) for 24 weeks and housed i) by genotype (single-housed) or ii) with members of the other genotype in a shared microbial environment (co-housed). The IL-1RI-/- gut microbiome is dominant to WT, meaning that co-housed WT mice adopted the IL-1RI-/- microbiota profile. This is concomitant with greater body weight, hepatic lipid accumulation, adipocyte hypertrophy, and hyperinsulinemia in co-housed WT mice, compared to single-housed counterparts. These effects are most evident following HFD. Primary features of microbiome differences are Lachnospiraceae and Ruminococcaceae (known producers of SCFA).

Conclusion: Transfer of SCFA-producing microbiota from IL-1RI-/- mice highlights a new connection between diet, inflammatory signaling, and the gut microbiome, an association that is dependent on the nature of the dietary fat challenge.

Keywords: co-housing; diet-induced obesity; hepatosteatosis; high-fat diet; interleukin 1β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / metabolism*
  • Animals
  • Diet, High-Fat / adverse effects*
  • Fatty Acids, Volatile / metabolism
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology*
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism
  • Liver / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, Interleukin-1 Type I / genetics*
  • Receptors, Interleukin-1 Type I / metabolism
  • Signal Transduction

Substances

  • Fatty Acids, Volatile
  • IL1R1 protein, mouse
  • Receptors, Interleukin-1 Type I