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The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue

Rebecca C Schugar1, Diana M Shih2, Manya Warrier1

  • 1Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.

Cell Reports
|June 22, 2017
PubMed

Insights

The gut microbe-generated compound trimethylamine N-oxide (TMAO) is linked to obesity and type 2 diabetes. Reducing the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) protected mice against obesity.

Area of Science:

  • Microbiology
  • Metabolic disorders
  • Obesity research

Background:

  • Gut microbiota plays a crucial role in host energy metabolism and is implicated in obesity-associated disorders.
  • Trimethylamine N-oxide (TMAO) is a metabolite produced by gut microbes, and its role in metabolic diseases is under investigation.

Purpose of the Study:

  • To investigate the link between the gut microbiota-initiated TMAO-generating pathway and obesity and energy metabolism.
  • To explore the association of TMAO levels with type 2 diabetes and obesity traits.
  • To determine the role of flavin-containing monooxygenase 3 (FMO3) in obesity and adipose tissue beiging.

Main Methods:

  • Analysis of systemic TMAO levels in human clinical cohorts and the Hybrid Mouse Diversity Panel.
  • Investigating the effect of FMO3 knockdown or genetic deletion on obesity in mice.
  • Examining the regulatory role of FMO3 in white adipose tissue beiging using mouse and human studies.

Main Results:

  • Systemic TMAO levels strongly associated with type 2 diabetes in human cohorts.
  • Circulating TMAO levels correlated with obesity traits across different inbred mouse strains.
  • FMO3 inhibition or deletion conferred protection against obesity in mice.
  • FMO3 was found to negatively regulate the beiging of white adipose tissue.

Conclusions:

  • The TMAO-generating pathway initiated by gut microbiota is linked to obesity and impaired energy metabolism.
  • FMO3 is a key enzyme in TMAO production and plays a significant role in regulating body weight and adipose tissue function.
  • Targeting FMO3 may represent a potential therapeutic strategy for obesity and related metabolic disorders.
Keywords:
FMO3adiposediabetesflavin-containing monooxygenase 3microbiotanutritionobesity

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