Journal
CELL RESEARCH
Volume 27, Issue 11, Pages 1309-1326Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2017.126
Keywords
intermittent fasting; thermogenesis; vascular endothelial growth factor; adipose macrophage
Categories
Funding
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Banting & Best Diabetes Centre (BBDC)
- Centre for Healthy Active Kids (CHAK)
- Canadian Institutes of Health Research (CIHR)
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and Future Planning [2015R1A5A2009124]
- Hospital for Sick Children
- Canadian Diabetes Association
- National Research Foundation of Korea [2015R1A5A2009124] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.
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