Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota

Cell Metab. 2017 Oct 3;26(4):672-685.e4. doi: 10.1016/j.cmet.2017.08.019. Epub 2017 Sep 14.


While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.

Keywords: beige adipocytes; browning; every-other-day fasting (EODF); gut microbiota; intermittent fasting; metabolic syndrome; obesity; short-chain fatty acid.

MeSH terms

  • Adipose Tissue, Beige / metabolism*
  • Adipose Tissue, White / metabolism*
  • Animals
  • Energy Metabolism
  • Fasting*
  • Fatty Liver / complications
  • Fatty Liver / metabolism
  • Fatty Liver / microbiology
  • Fatty Liver / therapy
  • Fibroblast Growth Factors / metabolism
  • Gastrointestinal Microbiome*
  • Insulin Resistance
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / microbiology
  • Metabolic Syndrome / therapy
  • Mice, Inbred C57BL
  • Obesity / complications
  • Obesity / metabolism
  • Obesity / microbiology
  • Obesity / therapy*
  • Signal Transduction
  • Thermogenesis


  • fibroblast growth factor 21
  • Fibroblast Growth Factors