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

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 M.I. Hussein, Kyung Oh Doh, Chi Chung Hui, Hoon Ki Sung

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1309-1326
Number of pages18
JournalCell Research
Volume27
Issue number11
DOIs
Publication statusPublished - 1 Nov 2017
Externally publishedYes

Keywords

  • adipose macrophage
  • Intermittent fasting
  • thermogenesis
  • vascular endothelial growth factor

Cite this

Kim, K. H., Kim, Y. H., Son, J. E., Lee, J. H., Kim, S., Choe, M. S., Moon, J. H., Zhong, J., Fu, K., Lenglin, F., Yoo, J. A., Bilan, P. J., Klip, A., Nagy, A., Kim, J. R., Park, J. G., Hussein, S. M. I., Doh, K. O., Hui, C. C., & Sung, H. K. (2017). Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. Cell Research, 27(11), 1309-1326. https://doi.org/10.1038/cr.2017.126