3 years ago

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

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

Publisher URL: https://www.nature.com/articles/cr2017126

DOI: 10.1038/cr.2017.126

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