Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage
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 JG, Hussein SM, Doh KO, Hui CC, Sung HK
Cell research · 190 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Canadian Diabetes Association
- Government
- National Research Foundation
- Government
- National Research Foundation of Korea
- University or hospital
- Hospital for Sick Children
- Government
- Canadian Institutes of Health Research
- Government
- Natural Sciences and Engineering Research Council of Canada
- University or hospital
- Banting and Best Diabetes Centre, University of Toronto
- Grants
- National Research Foundation (2015R1A5A2009124); National Research Foundation of Korea (2015R1A5A2 009124)
Based on 7 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2017-10-17 · Cell Res · vol. 27 · issue 11 · pp. 1309–1326
- Publisher
- Springer Nature
- Cited
- 223 citations · more than 99% of similar papers · 8.7× the field average
- Impact
- Top 10% most cited in its field
- References
- 73 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Dietary Effects on Health · Adipose Tissue and Metabolism · Circadian rhythm and melatonin
- Keywords
- Adipose tissue, Thermogenesis, Endocrinology, Internal medicine, Biology, White adipose tissue, FGF21, Homeostasis, Metabolic syndrome, Brown adipose tissue, Obesity, Medicine, Fibroblast growth factor, Receptor
- MeSH
- macrophages, animals, humans, mice, obesity, vascular endothelial growth factor a, diet, fasting, macrophage activation, thermogenesis, homeostasis, male, adipose tissue, white, transcriptome
20 authors
From CA, KR, US
- Kyoung-Han KimUniversity of Ottawa; Hospital for Sick Children
- Yun Hye KimHospital for Sick Children
- Joe Eun SonHospital for Sick Children
- Ju Hee LeeUniversity of Toronto; Hospital for Sick Children
- Sarah KimHospital for Sick Children
- Min Seon ChoeHospital for Sick Children
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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