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SCIENCE JOURNAL

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

The effects of intermittent fasting on obesity and metabolic disorders.

OCT 17, 2017

Written by Kyoung-Han Kim, Yun Hye Kim, Joe Eun Son, Ju Hee Lee, Sarah Kim, Min Seon Choe, Joon Ho Moon, Jian Zhong, Kiya Fu, Florine Lenglin, Jeong-Ah Yoo, Philip J Bilan, Amira Klip, Andras Nagy, Jae-Ryong Kim, Jin Gyoon Park, Samer MI Hussein, Kyung-Oh Doh, Chi-chung Hui, Hoon-Ki Sung

View full article HERE.

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ABSTRACT

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 over expression 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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CONCLUSION

In summary, our data demonstrate that metabolic benefits of IF are largely mediated by adipose thermogenesis without overall caloric reduction. We showed that fasting-induced adipose-VEGF plays a key role in WAT browning through M2 macrophage activation. This finding is further supported by human adipose tissue gene expression analysis illustrating positive correlations between adipose-VEGF expression and both M2 macrophage and WAT browning. Together, the present study illustrates the role of IF-induced adipose-VEGF in remodeling the immunometabolic property of adipose tissue, highlighting the importance of eating pattern and physiological fasting duration to sustain metabolic homeostasis.