TY - JOUR
T1 - COVID-19 instigates adipose browning and atrophy through VEGF in small mammals
AU - Jing, Xu
AU - Wu, Jieyu
AU - Dong, Caijuan
AU - Gao, Juan
AU - Seki, Takahiro
AU - Kim, Changil
AU - Urgard, Egon
AU - Hosaka, Kayoko
AU - Yang, Yunlong
AU - Long, Siwen
AU - Huang, Ping
AU - Zheng, Junnian
AU - Szekely, Laszlo
AU - Zhang, Yuanting
AU - Tao, Wei
AU - Coquet, Jonathan
AU - Ge, Minghua
AU - Chen, Yuguo
AU - Adner, Mikael
AU - Cao, Yihai
PY - 2022/12
Y1 - 2022/12
N2 - Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3–7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature–adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.
AB - Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3–7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature–adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.
UR - http://www.scopus.com/inward/record.url?scp=85143635652&partnerID=8YFLogxK
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85143635652&origin=recordpage
U2 - 10.1038/s42255-022-00697-4
DO - 10.1038/s42255-022-00697-4
M3 - RGC 21 - Publication in refereed journal
C2 - 36482111
SN - 2522-5812
VL - 4
SP - 1674
EP - 1683
JO - Nature Metabolism
JF - Nature Metabolism
IS - 12
ER -
