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

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

Author information

1
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China. Electronic address: hnsdlgl@hunnu.edu.cn.
2
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3
The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
4
Department of Molecular Toxicology, The Pennsylvania State University, University Park, PA 16802, USA.
5
Mouse Metabolism Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
6
The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan 41001, China.
7
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gonzalef@mail.nih.gov.

Abstract

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

PMID:
28918936
PMCID:
PMC5668683
DOI:
10.1016/j.cmet.2017.08.019
[Indexed for MEDLINE]
Free PMC Article

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