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

Research output: Contribution to journalArticle

23 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 (US)
Pages (from-to)1309-1326
Number of pages18
JournalCell Research
Volume27
Issue number11
DOIs
StatePublished - Nov 1 2017

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Macrophage Activation
Thermogenesis
Vascular Endothelial Growth Factor A
Fasting
Homeostasis
White Adipose Tissue
Obesity
Caloric Restriction
Insurance Benefits
Macrophages
Diet

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. / Kim, Kyoung Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong Ah; Bilan, Philip J.; Klip, Amira; Nagy, Andras; Kim, Jae Ryong; Park, Jin; Hussein, Samer M.I.; Doh, Kyung Oh; Hui, Chi Chung; Sung, Hoon Ki.

In: Cell Research, Vol. 27, No. 11, 01.11.2017, p. 1309-1326.

Research output: Contribution to journalArticle

Kim, KH, Kim, YH, Son, JE, Lee, JH, Kim, S, Choe, MS, Moon, JH, Zhong, J, Fu, K, Lenglin, F, Yoo, JA, Bilan, PJ, Klip, A, Nagy, A, Kim, JR, Park, J, Hussein, SMI, Doh, KO, Hui, CC & Sung, HK 2017, 'Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage', Cell Research, vol. 27, no. 11, pp. 1309-1326. https://doi.org/10.1038/cr.2017.126
Kim, Kyoung Han ; Kim, Yun Hye ; Son, Joe Eun ; Lee, Ju Hee ; Kim, Sarah ; Choe, Min Seon ; Moon, Joon Ho ; Zhong, Jian ; Fu, Kiya ; Lenglin, Florine ; Yoo, Jeong Ah ; Bilan, Philip J. ; Klip, Amira ; Nagy, Andras ; Kim, Jae Ryong ; Park, Jin ; Hussein, Samer M.I. ; Doh, Kyung Oh ; Hui, Chi Chung ; Sung, Hoon Ki. / Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. In: Cell Research. 2017 ; Vol. 27, No. 11. pp. 1309-1326.
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